Gene Therapy For Cervical Cancer Using Adenovirally Delivered Tissue Inhibitor Of Metalloproteinases-3

Excessive degradation and remodeling of the extracellular matrix (ECM) is one of the hallmarkers of cancer progression at nearly every step from the first breakdown of the basal membrane of a primary tumor up to the extended growth of established metastases. Matrix metalloproteinases (MMPs) is the most important proteases in ECM turn over, and many tumors have high levels of MMPs. The activities of MMPs can be inhibited by tissue inhibitors of metalloproteinases (TIMPs), which are the endogenous and specific inhibitors of MMPs. As a new member of the TIMPs family, TIMP-3 has several unique properties that set it apart from other TIMPs, including its ability to induce apoptosis and inhibit angiogenesis in many tumors.In this study, we measured the expression of TIMP-3 mRNA by RT-PCR and TIMP-3 protein by Western Blotting in three cervical cancer cell lines CaSKi, HeLa and C33a. The lowest level was detected in CaSKi whose ability of invasion was strongest in vitro assay, which suggested that decreased expression of TIMP-3 correlated with invasive activity and metastasis.Using Ad-GFP, we evaluated the susceptibility of adenovirus transduction in cervical.cancer, endometrial cancer, and.ovarian cancer. By means of observation of green fluorescence expression under fluorescentce microscope, the images suggested that these three types of gynecologic neoplasm were all susceptible to adenovirus transfer, but cervical cancer cells, especially these carrying high risk human papillomavirus (HPV) genome cells were the most...