Carcinoma Cell-Based Extracellular Matrix Modulates Cancer Cell Communication

The extracellular matrix (ECM) is a non-cellular dynamic complex forming a 3D spatial network influencing every cell present in the microenvironment. ECM proteins not only provide scaffolding systems for cells, but they also mediate their functions through cell-cell and cell-ECM interactions. Various tissue-mimicking culture systems or 3D tumor models for tumor studies have been advanced using collagen I, Matrigel, ECM and other biomaterials. The ECM secreted by cancer-associated fibroblasts (CAFs) has been studied for its contribution to tumor growth and its significant role in tumor microenvironment, however, ECM deposited by cancer cells has not been studied in detail. This study examined the role of the ECM derived from a TNBC cell line in cancer cell communications. The decellularized ECM of MDA-MB-231 cells has been prepared and used as the cancer ECM (cECM). The cECM hydrogel was prepared and its 3D spatial network was compared to that of collagen I and Matrigel. Cellular activities of MDA-MB-231 cells in cECM, such as proliferation, migration, cell-cell and cell-ECM interactions were compared to collagen I and Matrigel. E-cadherin as a cell-cell interaction marker, and FAK and α3β1 integrin as cell-ECM interaction markers were considered. Their expression by MDA-MB-231 (MM231) cells in different ECMs were subsequently analyzed. Human umbilical vein endothelial cells (HUVECs) were included in this study to observe the role of cECM in their growth since the tumor microenvironment generates many blood vessels. We found that cECM had modulated cell-cell and cell-matrix interactions for the formation of the tumor microenvironment.