Abstract 237: MET receptor is a potential new target for cervical carcinoma treatment

Abstract

Abstract Introduction: Cervical carcinoma (CC) is the major cause of death among women suffering from neoplastic disease especially in the developing countries. The highest mortality is observed in patients with late diagnosis and metastatic disease. MET protooncogene encodes a tyrosine kinase receptor for hepatocyte growth factor (HGF). MET activation triggers a complex biological program including stimulation of cell proliferation, motility and protection from apoptosis. This program plays an important role during embryonic development and wound healing, but abnormal MET activity contribute to cancer development and progression. Therefore, new therapeutic strategies inhibiting MET signaling have been sought. Objectives: The aim of this study was to examine the influence of MET inhibition on growth and metastatic ability of cervical carcinoma cell. Materials and Methods: CC cell line (HTB35) was transduced with MET shRNA and LacZ shRNA expressing viruses and selected with blasticidin. To check genes expression real-time PCR, western blot and flow cytometry were used. Proliferation, cell cycle and apoptosis was studied. Stress fibers organization, adhesion and migration were evaluated using using falloidin staining, adhesion assay and chemotaxis assay respectively. The level of various protein phosphorylation was estimated by western blot. Results: We showed that downregulation of MET expression in HTB-35 cell line causes: (i) the reduction in cell proliferation resulting from altered cell cycle progression, but not from enhanced apoptosis, (ii) changes in actin cytoskeleton organization, (iii) the increased expression of E-cadherin, (iv) the decrease of mRNA levels in the genes responsible for malignant phenotype (such as c-myc, CXCR4 and Slug), and (v) the increased expression of genes involved in EMT and metastasis (including Snail, Slug, Twist, MMP-2, MMP-9 and HIF-1α). Performed in vitro studies have not shown any significant effect of MET inhibition on adhesive ability of HTB-35 cervical carcinoma cell line. However, the decreased migration of MET negative cells was observed. Summary: Our results strongly, indicate that MET receptor plays an important role in stimulating growth and metastasis of HTB-35 cervical carcinoma cell line. Thus, inhibition of HGF-MET receptor axis could be used in the future as the new therapeutic strategy to block cervical carcinoma development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 237. doi:10.1158/1538-7445.AM2011-237