ENDOTHELIAL-CELL CA2-CELL CONTACT AND MODULATES CELL-CELL ADHESION( INCREASES UPON TUMOR)

The signal transduction mechanisms involved in tumor cell adhesion to endothelial cells are still largely undefined. The effect of metastati c murine melanoma cell and human prostate carcinoma cell contact on cy tosolic [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-mum inert beads. A similar increase in endothelial cell [Ca2+] was observed with human neutrophils or monocyte-like lymphoma cells, b ut not with endothelial cells, red blood cells, and melanoma cell-cond itioned medium. The increase in endothelial cell [Ca2+] was not inhibi ted by extracellular Ca2+ removal. In contrast, endothelial cell pretr eatment with thapsigargin, which releases endoplasmic reticulum Ca2+ i nto the cytosol and depletes this Ca2+ store site, abolished the cytos olic [Ca2+] rise upon melanoma cell contact. Endothelial cell pretreat ment with the membrane-permeant form of the Ca2+ chelator bis-(O-amini ophenoxyl)ethane-N,N,N',N'-tetraacetic acid blocked the increase in cy tosolic [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 melan oma cell adhesion to the endothelial cells. Thus, tumor cell contact w ith endothelial cells induces a rapid Ca2+ release from endothelial in tercellular stores, which has a functional role in enhancing cell-cell adhesion.