ATTACHMENT CHARACTERISTICS AND INVOLVEMENT OF INTEGRINS IN ADHESION OF BREAST-CANCER CELL-LINES TO EXTRACELLULAR BONE-MATRIX COMPONENTS

Evidence is mounting that changes in the ability of cancer cells to ad here to extracellular matrices play a decisive role in metastatic spre ad. The mechanism underlying the preference of breast cancer cells to metastasize to bone is, however, poorly understood. We investigated th e expression and involvement of integrin adhesion receptors in the adh esion of breast cancer cells to bone matrix (constituents) in two in v itro attachment assays using RGD peptides and anti-integrin antibodies . Breast cancer cells adhered rapidly to extracellular bone matrix. Ad hesion of most cells to vitronectin, fibronectin, thrombospondin, oste opontin, and the fairly bone-specific bone sialoprotein was inhibited by the 200 mu g/ml GRGDS peptide. These data suggest that integrin adh esion receptors can modulate the attachment of breast cancer cells to bone matrix molecules. In accordance with these findings, we found tha t alpha(1)-alpha(5)(beta(1)) and alpha(v)(beta(3)) integrins were expr essed by mammary carcinoma cells. Highly tumorigenic MDA-MB-231 cells, which form osteolytic metastases in vivo, expressed relatively high l evels of alpha(2) beta(1), alpha(3) beta(1), alpha(5) beta(1), alpha(v ) beta(3) integrins, when compared to MCF-7, T47D, and ZR75-1 breast c ancer cells. Addition of function-blocking anti-alpha(2) beta(1), -alp ha(3) beta(1), -alpha(5) beta(1) and -alpha(v) beta(3) antibodies sign ificantly inhibited the adhesion of MDA-MB-231 breast cancer cells to bone matrices. In conclusion, our data suggest a possible role for bet a(1) and beta(3) integrin subfamily members in the establishment of sk eletal metastases in advanced breast cancer patients. Clearly, functio nal evidence is required; to understand the mechanisms involved in the development of skeletal metastases in breast cancer patients.