ArticleJournal of the National Cancer Institute2014
Therapeutic targeting of integrin αvβ6 in breast cancer.
Open access · hybridAbstract read
In one paragraph
Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Integrin ανβ6 Protein Expression and Prognosis in Solid Tumors: A Meta-Analysis.Molecular diagnosis & therapy · 2020Pooled it
- Immunohistochemical Evaluation of Integrin β6 Expression in Triple-Negative Breast Cancer as a Predictive Biomarker for Therapeutic and Diagnostic Radionuclides.Biomolecules · 2026Article
- Epithelial Integrins Coordinate Cellular Crosstalk Through the Regulation of Cytokines During Tissue Remodeling.International journal of molecular sciences · 2026Review
- Computational theranostics strategy for pancreatic ductal adenocarcinoma.Molecular diversity · 2026Article
- Unraveling the αVβ5-GLUT5 axis in breast cancer: linking extracellular matrix signaling to fructose metabolism: a scoping review.Molecular biology reports · 2026Article
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026Review
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- Anti-metastatic potential of flavonoids for the treatment of cancers: focus on epithelial-mesenchymal transition (EMT) process.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- TGF-β Signaling in Cancer: Mechanisms of Progression and Therapeutic Targets.International journal of molecular sciences · 2025Review
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- Cardiac Toxicity Under Concurrent Administration of Trastuzumab (Anti-HER2 Therapy) and Radiotherapy: Systematic Review and Meta-Analysis.Health science reports · 2025Review
- Blockade of αvβ6 and αvβ8 integrins with a chromogranin A-derived peptide inhibits TGFβ activation in tumors and suppresses tumor growth.Journal of experimental & clinical cancer research : CR · 2025Article
- Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.Cancer cell international · 2025Review
- A Review of Talin- and Integrin-Dependent Molecular Mechanisms in Cancer Invasion and Metastasis.International journal of molecular sciences · 2025Review
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity.Frontiers in oncology · 2025Article
- A trafficking regulatory subnetwork governs αScience advances · 2024Article
- Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.Molecular imaging and biology · 2024Article
- Nasal allergen and methacholine provocation tests influence co‑expression patterns of TGF‑β/SMAD and MAPK signaling pathway genes in patients with asthma.Experimental and therapeutic medicine · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 7 institutions in 2 countries.
Kate M MooreAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Gareth J ThomasAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Stephen W DuffyAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Jane WarwickAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Rhian GabeAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Patrick ChouAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Ian O EllisAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Andrew R GreenAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Syed HaiderAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Kellie BrouiletteAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Antonio SahaAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Sabari VallathAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Rebecca BowenAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Claude ChelalaAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Diana EcclesAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
William J TapperAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Alastair M ThompsonAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Phillip QuinlanAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Lee JordanAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Cheryl GillettAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Adam BrentnallAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Shelia VioletteAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Paul H WeinrebAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Jane KendrewAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Simon T BarryAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
Ian R HartAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
J Louise JonesAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
John F MarshallAffiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB). j.f.marshall@qmul.ac.uk.
Biogen (United States) · USQueen Mary University of London · GBCancer Research UK · GBGuy's Hospital · GBSouthampton General Hospital · GBNinewells Hospital · GBNottingham City Hospital · GB
Funding
Breast Cancer Now 2008MAYPR32Cancer Research UK 12008Cancer Research UK 17764Medical Research Council G0800825
Abstract
backgroundIntegrin αvβ6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of αvβ6 has yet to be elucidated in breast cancer.
methodsProtein expression of integrin subunit beta6 (β6) was measured in breast cancers by immunohistochemistry (n > 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of β6 in breast cell lines, the role of αvβ6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ≥ 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.
resultsHigh expression of either the mRNA or protein for the integrin subunit β6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of β6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P < .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.
conclusionsTargeting αvβ6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.
Indexed as
Molecular Targeted TherapyAnimalsAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleFlow CytometryGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansImmunohistochemistryIntegrinsKaplan-Meier EstimateAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine Kinasesintegrin alphavbeta6IntegrinsTrastuzumab
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