Abstract 969: Expression of membrane-type matrix metalloproteinases (MT-MMPS) in head and neck squamous cell carcinomas, a target for prodrug development
Authors: Rene Ankrah, Steve D. Shnyder, James A. McCaul, Phil A. Batman, Robert Falconer, Paul M. Loadman
Journal: Cancer Research (2017)

Abstract Introduction: Head and Neck Squamous Cell Carcinomas (HNSCC), a group of highly aggressive heterogeneous epithelial malignancies, are considered the fifth most common cancer with the seventh highest cancer mortality. Despite advances in treatment, low five-year survival rates of around 30% still remain. Several studies have implicated the actions of matrix metalloproteinases (MMPs) in HNSCC progression. Their role in mediating extracellular matrix remodeling is paramount to tumour progression, as they facilitate invasion, angiogenesis and metastasis. In contrast, expression of active MMPs in normal tissues is largely absent. MT1-MMP (MMP14) expression is known to correlate with poor clinical response in several tumour types, but little is known about the expression of other MT-MMPs in HNSCC. We have assessed the protein expression of the entire MT-MMP complement in matched tumour and normal tissues of clinical HNSCC cases by immunohistochemistry, supported by Western Blot and gene expression data and will ultimately demonstrate translation of protein expression into MT-MMP-specific proteolytic activity. Differential expression would support the development of prodrugs specifically activated in the tumour by MMPs. Methods: 32 clinical cases (matched normal &amp; tumour tissues) were assayed for gene expression of the 6 members of the MT-MMP family (MMP14,15,16,17,24,25). Expression profiling was carried out using quantitative real-time reverse transcription-PCR analysis. Analysis of protein expression used IHC on fixed sections used with monoclonal antibodies specific for MT1 to MT6 MMP and Western blot analysis with monoclonal antibodies optimized for western blotting. Results: The protein expression of all six MT-MMPs has been characterised in clinical HNSCC samples and related to matched normal tissue controls. A differential in gene and protein expression levels exists between the MT-MMP profiles across the normal and cancer tissues examined. MT1-, MT3- and MT6-MMP in particular were shown to be highly overexpressed at both gene and protein level in the majority of tumours. MT2, MT4 and MT5-MMP expression was low or undetectable in all normal tissue and low in tumour tissue Conclusion: The existence and demonstration of differential MT-MMP protein expression in HNSCC relative to normal tissues is a valuable tool for prodrug development. MT1-, MT3- and MT6-MMP are highly expressed in the majority of tumour samples compared to matched normal control tissue. However, further work to elucidate the proteolytic activity of the expressed proteins and therefore the proteolytic capacity of tumours is needed to determine the suitability of HNSCC for prodrug therapy. Citation Format: Rene Ankrah, Steve D. Shnyder, James A. McCaul, Phil A. Batman, Robert Falconer, Paul M. Loadman. Expression of membrane-type matrix metalloproteinases (MT-MMPS) in head and neck squamous cell carcinomas, a target for prodrug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 969. doi:10.1158/1538-7445.AM2017-969