ArticleOtolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery2014
Matrix-metalloproteinases in head and neck carcinoma-cancer genome atlas analysis and fluorescence imaging in mice.
Article in Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Matrix Metalloproteinases and Their Inhibitors as Potential Prognostic Biomarkers in Head and Neck Cancer after Radiotherapy.International journal of molecular sciences · 2023Review
- Expression of matrix metalloproteinases (MMPs)-2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)-1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection.Frontiers in veterinary science · 2022Article
- Review
- The Response of the Tongue Epithelial on Cigarette Smoke Exposure as a Risk Factor for Oral Cancer Development.European journal of dentistry · 2021Article
- mRNA Expression Analysis of E-Cadherin, VEGF, and MMPs in Gastric Cancer: a Pilot Study.Indian journal of surgical oncology · 2021Article
- Article
- Coordinated Regulation of Metabolic Transporters and Migration/Invasion by Carbonic Anhydrase IX.Metabolites · 2018Review
- Article
- Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides.Oral oncology · 2017Article
- RGD-Binding Integrins in Head and Neck Cancers.Cancers · 2017Review
- p63 drives invasion in keratinocytes expressing HPV16 E6/E7 genes through regulation of Src-FAK signalling.Oncotarget · 2017Article
- SensitiveTheranostics · 2017Article
- Article
- Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate.JAMA otolaryngology-- head & neck surgery · 2016Observational
- FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Combined TP53 mutation/3p loss correlates with decreased radiosensitivity and increased matrix-metalloproteinase activity in head and neck carcinoma.Oral oncology · 2015Article
- Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins.In vivo (Athens, Greece)Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
objective(1) Obtain matrix-metalloproteinase (MMP) expression profiles for head and neck squamous cell carcinoma (HNSCC) specimens from the Cancer Genomic Atlas (TCGA). (2) Demonstrate HNSCC imaging using MMP-cleavable, fluorescently labeled ratiometric activatable cell-penetrating peptide (RACPP). STUDY
designRetrospective human cohort study; prospective animal study.
settingTranslational research laboratory. SUBJECTS AND
methodsPatient clinical data and mRNA expression levels of MMP genes were downloaded from TCGA data portal. RACPP provides complementary ratiometric fluorescent contrast (increased Cy5 and decreased Cy7 intensities) when cleaved by MMP2/9. HNSCC-tumor bearing mice were imaged in vivo after RACPP injection. Histology was evaluated by a pathologist blinded to experimental conditions. Zymography confirmed MMP-2/9 activity in xenografts. RACPP was applied to homogenized human HNSCC specimens, and ratiometric fluorescent signal was measured on a microplate reader for ex vivo analysis.
resultsExpression of multiple MMPs including MMP2/9 is greater in patient HNSCC tumors than matched control tissue. In patients with human papilloma virus positive (HPV+) tumors, higher MMP2 and MMP14 expression correlates with worse 5-year survival. Orthotopic tongue HNSCC xenografts showed excellent ratiometric fluorescent labeling with MMP2/9-cleavable RACPP (sensitivity = 95.4%, specificity = 95.0%). Fluorescence ratios were greater in areas of higher tumor burden (P < .03), which is useful for intraoperative margin assessment. Ex vivo, human HNSCC specimens showed greater cleavage of RACPP when compared to control tissue (P = .009).
conclusionsHuman HNSCC tumors show increased mRNA expression of multiple MMPs including MMP2/9. We used RACPP, a ratiometric fluorescence assay of MMP2/9 activity, to show improved occult tumor identification and margin clearance. Ex vivo assays using RACPP in biopsy specimens may identify patients who will benefit from intraoperative RACPP use.
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