ArticleBreast cancer research : BCR2011
Prospective evaluation of serum tissue inhibitor of metalloproteinase 1 and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer.
Article in Breast cancer research : BCR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Carbonic Anhydrase IX Induces Human Osteosarcoma Cell Metastasis by Activating HSPA6 Expression Through the AMPK Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Cell-Free Carbonic Anhydrase IX mRNA in Urine as Biomarker for Urogenital Cancers: The Relationship Between Urinary Extracellular RNA and Tumor-Cell-Associated RNA.Current issues in molecular biology · 2024Article
- Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study.Breast cancer research : BCR · 2023Observational
- Carbonic Anhydrase IX in Tumor Tissue and Plasma of Breast Cancer Patients: Reliable Biomarker of Hypoxia and Prognosis.International journal of molecular sciences · 2023Article
- Circulating proteins as predictive and prognostic biomarkers in breast cancer.Clinical proteomics · 2022Review
- Inhibition of Carbonic Anhydrase IX Suppresses Breast Cancer Cell Motility at the Single-Cell Level.International journal of molecular sciences · 2021Article
- Regulation of Tumor Metabolism and Extracellular Acidosis by the TIMP-10-CD63 Axis in Breast Carcinoma.Cells · 2021Article
- Carbonic anhydrase IX as a novel candidate in liquid biopsy.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Review
- Impairment of carbonic anhydrase IX ectodomain cleavage reinforces tumorigenic and metastatic phenotype of cancer cells.British journal of cancer · 2020Article
- The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer.Scientific reports · 2019Article
- Article
- Molecular docking based virtual screening of carbonic anhydrase IX with coumarin (a cinnamon compound) derived ligands.Bioinformation · 2019Article
- Dampness-Heat Accelerates DMBA-Induced Mammary Tumors in Rats.Chinese journal of integrative medicine · 2018Article
- Elevated serum RAS p21 is an independent prognostic factor in metastatic breast cancer.BMC cancer · 2018Observational
- Fibrosis as measured by the biomarker, tissue inhibitor metalloproteinase-1, predicts mortality in Age Gene Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study.European heart journal · 2017Article
- Sinomenine hydrochloride inhibits breast cancer metastasis by attenuating inflammation-related epithelial-mesenchymal transition and cancer stemness.Oncotarget · 2017Article
- Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor patients.Oncology letters · 2016Article
- Apoptosis-induced ectodomain shedding of hypoxia-regulated carbonic anhydrase IX from tumor cells: a double-edged response to chemotherapy.BMC cancer · 2016Article
- Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer.Disease markers · 2016Article
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Authors and funding
12 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCirculating tumor cells (CTCs) reflect aggressive tumor behavior by hematogenous tumor cell dissemination. The tissue inhibitor of metalloproteinase 1 (TIMP-1) plays a role in tissue invasion and is also involved in angiogenesis, abrogation of apoptosis and in chemoresistance. Carbonic anhydrase IX (CAIX) is a metalloenzyme involved in cell adhesion, growth and survival of tumor cells. The aim of the study was to investigate whether serum concentrations of TIMP-1 and CAIX are associated with the detection of CTC in metastatic breast cancer.
methodsBlood was obtained in a prospective multicenter setting from 253 patients with metastatic breast cancer at the time of disease progression. Serum TIMP-1 and CAIX were determined using commercial ELISA-kits (Oncogene Science). CTC were detected with the CellSearch system (Veridex).
resultsFive or more CTCs were detected in 122 patients out of 245 evaluable patients (49.8%). Out of 253 metastatic patients 70 (28%) had serum TIMP-1 levels above 454 ng/mL. Serum CAIX was elevated above 506 ng/mL in 90 (35%) patients. Both serum markers had prognostic significance. Median progression free survival (PFS) was 7.2 months with elevated TIMP-1 vs. 11.4 months with non-elevated levels (p < 0.01). OS was 11.5 vs. 19.1 months (p < 0.01). Median PFS was 7.5 months with elevated CAIX vs. 11.7 months with non-elevated levels (p < 0.01), overall survival (OS) was 13.4 months vs. 19.1 months (p < 0.01). In patients with five or more CTCs, serum levels were above the cut-off for CAIX in 47% vs. 25% in those with less than five CTCs (p = 0.01). For TIMP-1, 37% patients with five or more CTCs had elevated serum levels and 17% of patients with less than five CTCs (p = 0.01). Including TIMP-1, CAIX, CTC and established prognostic factors in the multivariate analysis, the presence of CTCs, the therapy line and elevated CAIX remained independent predictors of OS.
conclusionsElevated serum levels of the invasion markers TIMP-1 and CAIX in metastatic breast cancer are prognostic markers and are associated with the presence of CTCs. Whether increased secretion of TIMP-1 and/or CAIX might directly contribute to tumor cell dissemination remains to be elucidated in further investigations.
trial registrationCurrent Controlled Trials: ISRCTN59722891.
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