Endothelial cell Ca2+ increases upon tumor cell contact and modulates cell-cell adhesion.
The signal transduction mechanisms involved in tumor cell adhesion to endothelial cells are still largely undefined. The effect of metastatic murine melanoma cell and human prostate carcinoma cell contact on cytosolic [Ca2+] of bovine artery endothelial cells was examined in indo-1-loaded endothelial cell monolayers. A rapid increase in endothelial cell [Ca2+] occurred on contact with tumor cells, but not on contact with 8-microns inert beads. A similar increase in endothelial cell [Ca2+] was observed with human neutrophils or monocyte-like lymphoma cells, but not with endothelial cells, red blood cells, and melanoma cell-conditioned medium. The increase in endothelial cell [Ca2+] was not inhibited by extracellular Ca2+ removal. In contrast, endothelial cell pretreatment with thapsigargin, which releases endoplasmic reticulum Ca2+ into the cytosol and depletes this Ca2+ store site, abolished the cytosolic [Ca2+] rise upon melanoma cell contact. Endothelial cell pretreatment with the membrane-permeant form of the Ca2+ chelator bis-(O-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid blocked the increase in cytosolic [Ca2+]. Under static and dynamic flow conditions (0.46 dyn/cm2) bis-(O-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid pretreatment of bovine pulmonary artery endothelial cell monolayers inhibited melanoma cell adhesion to the endothelial cells. Thus, tumor cell contact with endothelial cells induces a rapid Ca2+ release from endothelial intracellular stores, which has a functional role in enhancing cell-cell adhesion.
Pili
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Cell Biology Unit, National Institute on Aging, National Institutes on Health, Baltimore, Maryland 21224.
Corda
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S
Passaniti
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A
Ziegelstein
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RC
Heldman
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AW
Capogrossi
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MC
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology; D005456:Fluorescent Dyes; D006801:Humans; D007211:Indoles; D007700:Kinetics; D008297:Male; D008546:Melanoma, Experimental / Q000503:physiopathology*; D051379:Mice; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011651:Pulmonary Artery; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D007211:Indoles; D004533:Egtazic Acid; C048960:indo-1; D002118:Calcium