INTEGRIN ALPHA(3)BETA(1) CAN PROMOTE ADHESION AND SPREADING OF METASTATIC BREAST-CARCINOMA CELLS ON THE LYMPH-NODE STROMA

We have reported that metastatic human melanoma cells utilize the alph a(v) beta(3) integrin to adhere to lymph node vitronectin (VN). In the present study, the adhesion of human and rat breast carcinoma cells t o lymph node tissue was analyzed. We have previously shown a correlati on between the metastatic potential of breast carcinoma cells and an R GD-mediated adhesion to cryostat sections of peripheral lymph nodes; t his adhesion could be blocked by an antibody to the integrin beta(1) s ubunit. Here, we show that the metastatic breast carcinoma cells were significantly more adherent to fibronectin (FN) expressed by lymph nod e-derived stromal cells than nonmetastatic cells. Metastatic cells als o spread more rapidly than non-metastatic cells on FN-coated substrate s. Using a combination of immunofluorescence microscopy, immunoprecipi tation and blocking assays with integrin-specific antibodies, we found (i) that expression of the alpha(3) beta(1) integrin on metastatic: m ammary carcinoma cells was specifically increased in comparison to non -metastatic cells and (ii) that the alpha(3) beta(1) receptor was invo lved in the increased adhesion of metastatic cells to lymph node FN an d in cell spreading on FN-coated substrates. Our data also suggest tha t the alpha(5) beta(1) integrin, which is also expressed on the metast atic cells, did not contribute to this increase in adhesion. Our data implicate the alpha(3) beta(1) integrin in adhesion to lymph node stro mal cell FN and suggest that metastatic cells of different tissue orig ins (e.g., melanoma and breast carcinoma) may utilize distinct integri n-ligand combinations to colonize the same target organ. (C) 1996 Wile y-Liss, Inc.