Localization and activity of calmodulin is involved in cell-cell adhesion of tumor cells and endothelial cells in response to hypoxic stress.
Cell Biol Toxicol
; 23(5): 323-35, 2007 Sep.
Article
in En
| MEDLINE
| ID: mdl-17351827
ABSTRACT
Adhesion of tumor cells to endothelial cells is known to be involved in the hematogenous metastasis of cancer, which is regulated by hypoxia. Hypoxia is able to induce a significant increase in free intracellular Ca2+ levels in both tumor cells and endothelial cells. Here, we investigate the regulatory effects of calmodulin (CaM), an intracellular calcium mediator, on tumor cell-endothelial cell adhesion under hypoxic conditions. Hypoxia facilitates HeLa cell-ECV304 endothelial cell adhesion, and results in actin cytoskeleton rearrangement in both endothelial cells and tumor cells. Suppression of CaM activation by CaM inhibitor W-7 disrupts actin cytoskeleton organization and CaM distribution in the cell-cell contact region, and thus inhibits cell-cell adhesion. CaM inhibitor also downregulates hypoxia-induced HIF-1-dependent gene expression. These results suggest that the Ca2+ -CaM signaling pathway might be involved in tumor cell-endothelial cell adhesion, and that co-localization of CaM and actin at cell-cell contact regions might be essential for this process under hypoxic stress.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calmodulin
/
Endothelial Cells
/
Hypoxia-Inducible Factor 1
/
Hypoxia
Limits:
Humans
Language:
En
Journal:
Cell Biol Toxicol
Journal subject:
TOXICOLOGIA
Year:
2007
Document type:
Article