Abstract

Abstract Cancer-associated fibroblasts (CAFs), as the major components of the tumor microenvironment (TME), have been extensively explored and are known to be involved in tumor biology, including growth, energy metabolism, immune regulation, invasion and metastasis. A large number of preclinical studies describe the functional and biochemical impact of commonly used chemotherapeutics, such as paclitaxel and oxaliplatinum, on cancer cells, but their effect on the phenotypical and biochemical changes of CAFs and their reciprocal impact on tumor progression are lacking. In our study, we used patient-derived breast and colorectal CAF to evaluate dose-response effects of paclitaxel and oxaliplatinum, respectively first-line chemotherapeutics in breast and colorectal cancer. We evaluated the damage responses of CAF and investigated changes in morphology, cell death, woundhealing migration, type I collagen contraction and invasion, cytokine and chemokine release, differential protein expression, and metabolic activity. In response to paracrine signals emerging from chemotherapy-treated CAF we investigated the impact on functional activity of macrophages, neutrophils and cancer cells. Our project could help us better understand and modulate the activity of CAFs, which might provide novel targets for the clinical treatment of cancer. Citation Format: Zihan Xia, Olivier De Wever. Impact of chemotherapy on functional and biochemical characteristics of cancer-associated fibroblasts​ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1362.

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