The role of
tumor cell adhesion in
lymphatic metastasis of
breast cancer was investigated in vitro using a rat mammary
carcinoma model of four cell lines with different metastatic phenotypes, two human
breast cancer cell lines, and cryostast sections of normal rat or human lymph nodes, respectively. A positive correlation was found between the adhesion levels obtained with three metastatic rat mammary cell lines (TMT-081 greater than MT-100M & TMT-50) and a non-metastatic line MT-W9B, the latter being 3-4 fold less adhesive to the lymph node sections than the metastatic
tumors. This selective adhesion was specific, as it was not found with cryostat sections of rat liver and brain.
Enzyme assays indicated that
cell surface glycoproteins bearing terminal
beta-galactoside residues were involved in the adhesion of the rat
tumors. Adhesion of the human
breast carcinoma cells Hs578T to sections of human lymph nodes was significantly higher than that of the normal breast epithelial cell line Hs578Bst, and comparable to adhesion of a second
breast carcinoma line, MCF-7. Moreover, Hs578T cells isolated from regional lymph nodes of
tumor-bearing nude mice were significantly more adhesive to human lymph node sections than the parental line. Adhesion of both human and rat
tumors could be partially blocked by the addition of the synthetic
peptide GRGDSPK and by
antibodies directed to the beta 1 chain of
integrin, suggesting that an
integrin receptor may played a role in the adhesion. The results suggest that
tumor cell adhesion to cryostat sections of lymph nodes is a correlate of the malignant phenotype in mammary
tumors of diverse origins, and could be used to delineate the adhesion factors mediating
lymphatic metastasis.