ROLE OF BETA-1 INTEGRINS IN ORGAN SPECIFIC ADHESION OF MELANOMA-CELLS INVITRO

BACKGROUND: Recent data suggest that the extracellular matrix of organs and heterogeneous integrin expression of tumor cells may influence metastasis distribution. EXPERIMENTAL DESIGN: Three human melanoma cell lines were characterized for integrin expression, in vitro binding to cryostat sections of different organs, and ability to generate experimental metastases in triple immunodeficient mice. RESULTS: The three cell lines exhibited heterogeneous expression of integrins, binding to cryostat sections, and organ colonization. A primary melanoma cell line (PM-WK) did not give rise to experimental metastases, showed scant or mild attachment to only a few organ tissue sections, and showed absent or minimal expression of alpha-integrin subunits tested (VLA 1-6) and alphavbeta3. In contrast, two lymph node derived lines exhibited distinct patterns of organ colonization: MM-RU colonized only the lungs and expressed predominantly alpha2beta1 and alphavbeta3 integrin, whereas MM-AN colonized lung and extrapulmonary sites including pancreas and subcutaneous brown fat and expressed predominantly alpha2beta1 and alpha6beta1 integrin. In vitro, MM-RU exhibited marked attachment to lung, brown fat, kidney, and adrenal with no binding to liver, pancreas, brain, or muscle tissue sections, whereas MM-AN had a similar binding profile but with additional attachment to liver and pancreas. Function blocking anti-beta1 monoclonal antibody inhibited the attachment of MM-RU and MM-AN cells to these tissues (p < 0.001), whereas function blocking anti-alpha5 and an unrelated monoclonal antibody (HLA class 1) did not. Function blocking anti-alpha2 monoclonal antibody inhibited MM-RU cell adhesion (p < 0.001) but not MM-AN adhesion. However, the function blocking monoclonal antibody alpha6beta1 significantly inhibited the binding of MM-AN to these tissues. CONCLUSIONS: These data suggest that alpha2beta1 and alpha6beta1 mediate differential melanoma cell attachment to organ tissue sections in vitro and that differences in integrin expression of these melanoma cells may be involved in differential organ colonization in vivo.