Analysis of cell matrix adhesions in a biomimetic extracellular matrix model for breast cancer invasion across tissue interfaces

To form metastases in distant tissues, invasive tumor cells must first migrate into the tissue surrounding the primary solid tumor and cross defined tissue interfaces. These are caused by changes in the extracellular matrix (ECM) generated by tumor-associated cells, among other things. The migrating neoplastic cell is exposed to a local drop-in ECM density and stiffness, which can significantly alter the extracellular biophysical signals affecting the cell and can influence the gene expression pattern. 3D collagen-I matrices, which represent the different topological and mechanical properties of the spatially adjacent tissues, were used to study the behavior of tumor cells after crossing such tissue interfaces. So-called step gradient matrices, consisting of two compartments with different porosities in direct contact via a defined interface, were used for this. In the present work, embedding the highly invasive breast cancer cell line MDA-MB-231 in the denser compartment could show that exogenous mechanical stimuli change when crossing clearly defined interfaces into a more open compartment. Different Integrin cluster intensities could be detected with immunostaining. There was evidence for activated mechanotransductive signaling in the highly invasive breast cancer cells MDA-MB-231 during interface crossing. Overall, this work proved that step gradient matrices are well suited as an in vitro model to investigate the invasion of cells from the primary tumor into the surrounding healthy tissue. In the future, it makes sense to use this model for other types of cancer to study cell behavior during the invasion process.