Competitive enhancement of HGF-induced epithelial scattering by accessory growth factors.

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Competitive enhancement of HGF-induced epithelial scattering by accessory growth factors.

Exp Cell Res. 2011 Feb 1;317(3):307-18

Authors: Chung JY, Davis JA, Price BD, Staley DM, Wagner MV, Warner SL, Bearss DJ, Hansen MD

Abstract
HGF signaling induces epithelial cells to disassemble cadherin-based adhesion and increase cell motility and invasion, a process termed epithelial-mesenchymal transition (EMT). EMT plays a major role in cancer metastasis, allowing individual cells to detach from the primary tumor, invade local tissue, and colonize distant tissues with new tumors. While invasion of vascular and lymphatic networks is the predominant route of metastasis, nerves also can act as networks for dissemination of cancer cell to distant sites in a process termed perineual invasion (PNI). Signaling between nerves and invasive cancer cells remains poorly understood, as does cellular decision making that selects the specific route of invasion. Here we examine how HGF signaling contributes to PNI using reductionist culture model systems. We find that TGF?, produced by PC12 cells, enhances scattering in response to HGF stimulation, increasing both cell-cell junction disassembly and cell migration. Further, gradients of TGF? induce migratory mesenchymal cells to undergo chemotaxis towards the source of TGF?. Interestingly, VEGF suppresses TGF?-induced enhancement of scattering. These results have broad implications for how combinatorial growth factor signaling contributes to cancer metastasis, suggesting that VEGF and TGF? might modulate HGF signaling to influence route selection during cancer progression.

PMID: 21075102 [PubMed - indexed for MEDLINE]

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