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. 2020 Oct 6;20:960. doi: 10.1186/s12885-020-07274-6

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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