Role of beta-1 integrins in organ specific adhesion of melanoma cells in vitro.
BACKGROUND
Recent data suggest that the extracellular matrix of organs and heterogeneous integrin expression of tumor cells may influence metastasis distribution.


METHODS
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.
Vink
J
J
Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston.
Thomas
L
L
Etoh
T
T
Bruijn
J A
JA
Mihm
M C
MC
Gattoni-Celli
S
S
Byers
H R
HR
D000818:Animals; D002448:Cell Adhesion; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D008545:Melanoma / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D014407:Tumor Cells, Cultured
D019012:Integrin beta1; D016023:Integrins