Fig. 10

Proposed model of TIMP-2 inhibition in ovarian cancer cells. a Effect of TIMP-2 inhibition on proliferation and invasion: High-grade ovarian tumours overexpress TIMP-2. However, TIMP-2 inhibition increases proliferation and invasion of ovarian cancer cells. It is postulated to occur through enhancement in the expression of MT1-MMP, which facilitates ECM remodelling through downregulation of E-Cadherin expression, degradation of COL12A1 and upregulation of N-Cadherin and Vimentin. b Effect of TIMP-2 inhibition on chemoresistance: Chemotherapy treatment enhances TIMP-2 enriched CSC-like cells. We hypothesise that under the current conventional treatment protocol, which consists of platinum and taxane-based drugs most patients treated with chemotherapy undergo consecutive recurrences due to development of chemoresistant tumours enriched in TIMP-2 and CSCs. However, if the patients are treated with conventional chemotherapy in combination with STAT3 inhibitors or therapies that reduce TIMP-2 expression, this can eradicate CSCs during the first line of treatment, and/or subsequent lines of treatments. This consequently would lead to a decreased tumour burden with increased disease free survival periods and better treatment outcomes in ovarian cancer patients