IN-VIVO EVIDENCE OF THE ROLE OF ALPHA(4)BETA(1)-VCAM-1 INTERACTION INSARCOMA, BUT NOT IN CARCINOMA EXTRAVASATION

Tumor-cell invasion can occur via either lymphatics or blood vessels. When in the blood circulation, tumor cells have to adhere to endotheli um lining the blood vessels before they can extravasate. Several famil ies of adhesion molecules have been recognized: selectins and their ol igosaccharide-containing ligands and integrins and their counter-recep tors belonging to the immunoglobulin superfamily. Besides their essent ial role in leukocyte extravasation, these adhesion molecules have bee n proposed by in vitro experiments to be involved in tumor-cell invasi on by facilitating the adhesion of malignant cells to endothelium lead ing to extravasation and metastasis. We have previously shown that, in vitro, several sarcoma cell lines adhere strongly to cultured endothe lial cells via alpha(4) beta(1)-VCAM-1 interaction. Here we show that sarcoma cells, especially in the metastatic lesions, were strongly alp ha(4) beta(1) positive but did not express alpha(4) beta(7), which is another receptor vor VCAM-1. Furthermore, we demonstrate that the capi llary endothelium within metastatic sarcoma lesions reacted strongly w ith anti-VCAM-1 antibody and very often the alpha(4) beta(1)-expressin g sarcoma cells were localized in the close vicinity of VCAM-1-express ing vessels. As control material we analyzed carcinoma specimens, but could not detect any alpha(4)-integrin expression on malignant cells e ven though the endothelial cells were often VCAM-1 positive. These res ults suggest that carcinomas do not use alpha(4) beta(1)-VCAM-1 in ext ravasation and, taken together, provide circumstantial evidence that i n vitro findings of alpha(4) beta(1)-VCAM-1-dependent sarcoma cell adh esion to endothelium can be extended to in vivo situations. (C) 1994 W iley-Liss, Inc.