Endothelial cell damage by Walker carcinosarcoma cells is dependent on vitronectin receptor-mediated tumor cell adhesion.
The transport of cancer cells from blood vessels to extravascular tissue is a critical step in metastasis, where endothelial cells and the vascular basement membrane act as barriers to cell traffic. Because endothelial injury can facilitate the metastasis of intravascular cancer cells in vivo, the authors have studied in vitro the free-radical-mediated endothelial damage caused by the rat Walker 256 carcinosarcoma (W256) cell after stimulation with 10(-6) mol/l (molar) phorbol ester. Here the authors have examined the hypothesis that W256 cell-mediated endothelial injury is dependent on adhesion between the effector and target cells. Attachment of phorbol 12-myristate, 13-acetate (PMA)-stimulated W256 cells to endothelial monolayers was increased 1.8 +/- 0.1-fold and damage (3H-2-deoxyglucose release from labeled endothelium) 1.4 +/- 0.1-fold after 4-hour pretreatment of the endothelium with 10 ng/ml recombinant human interleukin-1 alpha (rIL-1 alpha). Under various assay conditions, the release of 3H-2-deoxyglucose correlated directly with tumor cell adhesion (r = 0.98, P less than 0.005). In the presence of a polyclonal anti-vitronectin receptor antiserum, adhesion of stimulated W256 cells to rIL-1 alpha-treated monolayers was inhibited by 39% +/- 2%, and 3H-2-deoxyglucose release was inhibited by 53% +/- 13%. Immunoblot analysis and immunofluorescence flow cytometry demonstrated that the endothelial cells but not the W256 cells expressed vitronectin receptor (VnR) on their cell surface. The surface expression of VnR by endothelial cells was increased 1.9 +/- 0.1-fold after 4 hours' incubation with rIL-1 alpha. The authors conclude that W256 cell-mediated endothelial damage is dependent on cell adhesion, which, in turn, is partly regulated by the expression of VnR on the endothelial cell surface.
Shaughnessy
S G
SG
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Lafrenie
R M
RM
Buchanan
M R
MR
Podor
T J
TJ
Orr
F W
FW
D000818:Animals; D002296:Carcinosarcoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002448:Cell Adhesion / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D007106:Immune Sera / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology*; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007106:Immune Sera; D007375:Interleukin-1; D011971:Receptors, Immunologic; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; D003847:Deoxyglucose; D013755:Tetradecanoylphorbol Acetate