IMR Press / FBL / Volume 10 / Issue 2 / DOI: 10.2741/1643

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Involvement of phospholipase C signaling in melanoma cell-induced endothelial junction disassembly
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1 Department of Bioengineering, the Pennsylvania State University, University Park, PA, USA
2 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC
3 Department of Veterinary Science, The Pennsylvania State University, University Park, PA

Academic Editor: Cheng Dong

Front. Biosci. (Landmark Ed) 2005, 10(2), 1597–1606; https://doi.org/10.2741/1643
Published: 1 May 2005
(This article belongs to the Special Issue Cellular biomechanics)
Abstract

In this study, we report a phospholipase C (PLC)-mediated mechanism for the redistribution of interendothelial adherens junctions in response to melanoma cell contacts with the endothelium. We demonstrated that contact of melanoma cells to human umbilical vein endothelial cells (HUVEC) triggered rapid endothelial [Ca2+]i response through PLC-IP3 pathway. In addition, alternation of endothelial adherens junctions following contact of melanoma cells was evidenced by the changes in immunological staining patterns of vascular endothelial (VE)-cadherin. A PLC inhibitor, U73122 was shown to significantly diminish [Ca2+]i response and reduce the occurrence of melanoma cell-induced VE-cadherin reorganization. Moreover, inhibition of PLC attenuated melanoma cell transendothelial migration. However, melanoma cell-associated VE-cadherin breakdown was not sensitive to Ly294002, an inhibitor of phosphatidylinositol-3-kinase (PI3K), whereas inhibition of PI3K resulted in a reduction of melanoma cell transmigration. Taken together, our findings implicate that by inducing the PLC-Ca2+ signaling pathway, melanoma cells disrupt EC junctions to breach the endothelium and promote transvascular homing of tumor cells.

Keywords
Endothelial adherens junction
intracellular calcium
signaling
tumor cell migration
vascular endothelial-cadherin
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