Role of beta-1 integrins in organ specific adhesion of melanoma cells in vitro

Abstract

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 alpha v beta 3. In contrast, two lymph node derived lines exhibited distinct patterns of organ colonization: MM-RU colonized only the lungs and expressed predominantly alpha 2 beta 1 and alpha v beta 3 integrin, whereas MM-AN colonized lung and extrapulmonary sites including pancreas and subcutaneous brown fat and expressed predominantly alpha 2 beta 1 and alpha 6 beta 1 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-beta 1 monoclonal antibody inhibited the attachment of MM-RU and MM-AN cells to these tissues (p < 0.001), whereas function blocking anti-alpha 5 and an unrelated monoclonal antibody (HLA class I) did not. Function blocking anti-alpha 2 monoclonal antibody inhibited MM-RU cell adhesion (p < 0.001) but not MM-AN adhesion. However, the function blocking monoclonal antibody alpha 6 beta 1 significantly inhibited the binding of MM-AN to these tissues.

Conclusions: These data suggest that alpha 2 beta 1 and alpha 6 beta 1 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.