Abstract
Cellular fibronectin (FN) and tenascin-C (TNC) are prominent development- and disease-associated matrix components with pro- and anti-adhesive activity, respectively. Whereas both are present in the tumour vasculature, their functional interplay on vascular endothelial cells remains unclear. We have previously shown that basally-oriented deposition of a FN matrix restricts motility and promotes junctional stability in cultured endothelial cells and that this effect is tightly coupled to expression of FN. Here we report that TNC induces FN expression in endothelial cells. This effect counteracts the potent anti-adhesive activity of TNC and leads to the assembly of a dense highly-branched subendothelial matrix that enhances tubulogenic activity. These findings suggest that pro-angiogenic remodelling of the perivascular matrix may involve TNC-induced upregulation of FN in endothelial cells.
Highlights
Angiogenesis, the sprouting of new vasculature from a pre-existing vascular network, is an essential process during development, maintenance of tissues and metastatic spread of cancer
Some vessels displayed little or no FN staining and TNC appeared to be in direct contact with cells lining the vessels (Fig. 1, white arrow). Together these observations reflect the heterogeneity of the tumour vasculature and raise questions concerning the dynamic regulation of matrix protein expression by vascular endothelial cells
We found that TNC is not expressed in endothelial cells and exposure of cells to the immobilized protein stimulates expression and subendothelial assembly of autocrine FN
Summary
Angiogenesis, the sprouting of new vasculature from a pre-existing vascular network, is an essential process during development, maintenance of tissues and metastatic spread of cancer. This multi-step process is tightly regulated and spatiotemporally controlled by various soluble cytokines, membrane-bound proteins, cell-matrix and cell-cell interactions and hemodynamic forces. Through adhesive interactions with integrins expressed on the endothelial cell surface, the ECM orchestrates complex signalling cascades within the cells and affects many fundamental aspects of their biology, including proliferation, migration, cytoskeletal organization, cell shape, survival, and blood vessel stabilization (reviewed in[1]). We show that vascular endothelial cells respond to a direct anti-adhesive effect of TNC by enhancing FN expression and assembly
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