Tumor cell attachment to the vascular endothelium and subsequent degradation of the subendothelial extracellular matrix

Abstract

Highly metastatic variants of B16 melanoma exhibited a flattened morphology and decreased rate of melanogenesis when plated on a naturally produced subendothelial extracellular matrix (ECM) as compared with regular tissue culture plastic. The melanoma cells exhibited a much faster and firmer attachment to the ECM than they did to the apical surface of a confluent monolayer of vascular endothelial cells. Tumor cell interaction with the ECM was associated with degradation of its sulphated proteoglycans, as revealed by a release of low molecular weight (MW) degradation products upon incubation with metabolically [ 35S]O 4 = -labelled ECM. Agitation of the culture dishes, so as to better resemble the dynamics of blood flow and turbulence, greatly inhibited both tumor to endothelial cell attachment and subsequent degradation of the subendothelial ECM, but had only a partial inhibitory effect when the melanoma cells were seeded in direct contact with the ECM. Degradation of sulphated components of the ECM was not induced by purified preparations of either trypsin, collagenase, hyaluronidase or elastase. It is suggested that the ability of metastatic tumor cells to firmly adhere and degrade the proteoglycan scaffolding of the subendothelium leads to a destruction and dissolution of the basal lamina in areas adjacent to arrested tumor cells and thereby allows their successful extravasation.