Basement Membrane, Collagen, and Fibronectin: Physical Interactions with Cancer Cells

Cancer cell invasion is regulated by extracellular matrix (ECM) chemical signaling and gene expression but it also consists in a mechanical process controlled by ECM’s array. Scanning electron microscope analysis, invasion test, and real-time PCR demonstrated that Matrigel mimicking basement membrane (BM) doesn’t promote epithelial–mesenchymal transition (EMT) in both low and very aggressive breast cancer cells (MCF-7 and MDA-MB-231). A loose network of type I collagen mimicking the sub-BM favors EMT in MCF-7 cells but physically limits their invasion ability vs. Matrigel, as collagen does not induce an increase of metalloproteases (MMPs) in cells following ameboid-invasion mode. Collagen doesn’t change MDA-MB-231 phenotypes but further improves their invasion capability vs. Matrigel, by stimulating MMPs production. Concentrated type I collagen mimicking deeper ECM induces cells adhesion, further development of microvesicles, microvilli, long filopodia, and tunneling nanotubes (TNTs). Nonaligned fibronectin favors breast cancer cells adhesion, microvesicles, and TNTs development. Densely packed and parallel collagen fibers mimicking a collagen array in mammary tumor progression oppose invasion. In colon cancer, LoVo-R cells, resistant to doxorubicin, concentrated collagen favors development of invaginating phenotypes with invadopodia. We suggest that collagen acts as a physical factor inducing EMT in breast cancer cells and drug resistance in LoVo-R cells.