The relative roles of vitronectin receptor, E-selectin and alpha 4 beta 1 in cancer cell adhesion to interleukin-1-treated endothelial cells.
Adhesion of cancer cells to endothelium is thought to be a prerequisite to extravasation during the haematogenous phase of metastasis, and is enhanced after perturbation of the endothelium by interleukin-1 (IL-1). The inducible endothelial adhesion molecules, E-selectin, VCAM-1/alpha 4 beta 1 and vitronectin receptor have been reported to mediate attachment of cancer cells to IL-1-treated endothelial cells. We have examined the relative contribution of these molecules by quantifying the adhesion of a panel of 22 human, 125I-labelled cancer cells and the rat W256 tumour to untreated and IL-1-treated endothelial monolayers in the presence of relevant neutralising antibodies. Antibodies against E-selectin inhibited the adhesion of HL-60 leukaemia cells and two colon carcinomas. Anti-alpha 4 beta 1 antibodies blocked adhesion of four melanomas, five sarcomas and one lung carcinoma. Anti-vitronectin receptor antibodies inhibited adhesion of 14 of the 22 human cell lines to IL-1-treated endothelial cells. Adhesion of seven cell lines was inhibited by more than a single antibody. In contrast, adhesion of one of the cancer cell lines was unaffected by any of the antibodies, suggesting involvement of other IL-1-inducible endothelial adhesion molecules. Moreover, none of the antibodies altered the attachment of cancer cells to unstimulated endothelial monolayers. We conclude that the mechanisms of cancer cell adhesion to the endothelium are influenced by endothelial activation and by the adhesive repertoire of the cancer cell.
Lafrenie
R M
RM
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Gallo
S
S
Podor
T J
TJ
Buchanan
M R
MR
Orr
F W
FW
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D019040:E-Selectin; D004727:Endothelium / Q000187:drug effects; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D051381:Rats; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000502:physiology; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured / Q000502:physiology*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D039041:Integrin alpha4beta1; D016023:Integrins; D007375:Interleukin-1; D016024:Receptors, Cytoadhesin; D011971:Receptors, Immunologic; D016029:Receptors, Very Late Antigen; D019030:Receptors, Vitronectin