Covalent cross-linking of basement membrane-like matrices physically restricts invasive protrusions in breast cancer cells.

Covalent cross-linking of basement membrane-like matrices physically restricts invasive protrusions in breast cancer cells. Matrix Biol. 2019 Jun 01;: Authors: Wisdom KM, Indana D, Chou PE, Desai R, Kim T, Chaudhuri O Abstract The basement membrane (BM) provides a physical barrier to invasion in epithelial tumors, and alterations in the molecular makeup and structural integrity of the BM have been implicated in cancer progression. Invadopodia are the invasive protrusions that enable cancer cells to breach the nanoporous basement membrane, through matrix degradation and generation of force. However, the impact of covalent cross-linking on invadopodia extension into the BM remains unclear. Here, we examine the impact of covalent cross-linking of extracellular matrix on invasive protrusions using biomaterials that present ligands relevant to the basement membrane and provide a nanoporous, confining microenvironment. We find that increased covalent cross-linking of reconstituted basement membrane (rBM) matrix diminishes matrix mechanical plasticity, or the ability of the matrix to permanently retain deformation due to force. Covalently cross-linked rBM matrices, and rBM-alginate interpenetrating networks (IPNs) with covalent cross-links and low plasticity, restrict cell spreading and protrusivity. The reduced spreading and reduced protrusivity in response to low mechanical plasticity occurred independent of proteases. Mechanistically, ou...
Source: Matrix Biology - Category: Molecular Biology Authors: Tags: Matrix Biol Source Type: research