Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype.

Matrix remodeling maintains embryonic stem cell self-renewal by activating Stat3.

While a variety of natural and synthetic matrices have been used to influence embryonic stem cell (ESC) self-renewal or differentiation, and ESCs also deposit a rich matrix of their own, the mechanisms behind how extracellular matrix affects cell fate are largely unexplored. The ESC matrix is continuously remodeled by matrix metalloproteinases (MMPs), a process that we find is enhanced by the presence of mouse embryonic fibroblast feeders in a paracrine manner. Matrix remodeling by MMPs aids in the self-renewal of ESCs, as inhibition of MMPs inhibits the ability of ESCs to self-renew.

Attenuation of extrinsic signaling reveals the importance of matrix remodeling on maintenance of embryonic stem cell self-renewal.

The role of extrinsic factors in maintaining self-renewal of embryonic stem cells (ESCs) has been extensively studied since the cells' isolation, but the necessity for cell-secreted factors in self-renewal has remained undefined to date. Although it is generally accepted that addition of leukemia inhibitory factor (LIF) together with either serum or bone morphogenetic protein 4 (BMP4) is sufficient to maintain mouse ESCs (mESCs) in a self-renewing state, this does not preclude the possibility that autocrine factors are also required. Here we make use of a microfluidic perfusion device that is able to globally diminish diffusible autocrine signaling by applying continuous media flow to deplete cell-secreted factors.