B. Feldinghabermann et al., ROLE OF BETA-3 INTEGRINS IN MELANOMA CELL-ADHESION TO ACTIVATED PLATELETS UNDER FLOW, The Journal of biological chemistry, 271(10), 1996, pp. 5892-5900
Mechanisms mediating tumor cell attachment to the vessel wall under fl
ow conditions are largely unknown, Therefore we analyzed the ability o
f human melanoma cells to adhere to an immobilized matrix during blood
flow and determined the role of platelets in this process, In a paral
lel plate flow chamber, M21 melanoma cells were suspended in human blo
od and perfused over a collagen I matrix at a wall shear rate of 50 s(
-1) (2 dynes/cm(2)) to simulate venous flow over a thrombogenic surfac
e, Melanoma cell interaction with the matrix or blood cells and platel
ets was monitored and quantified by fluorescence and confocal laser mi
croscopy, Despite their ability to adhere to collagen I under static c
onditions, M21 cells failed to attach directly to this matrix during b
lood flow, However, they associated with adherent thrombi, and this re
sulted in stable melanoma cell arrest, Inhibition of platelet activati
on or platelet integrin alpha IIb beta 3 function abolished M21 cell a
ttachment, Melanoma cell interaction with thrombi was specific and req
uired beta 3 integrin expression, M21-L cells which lack integrin alph
a v beta 3 failed to associate with thrombi and to arrest during blood
flow, Transfection of these cells with the integrin subunits alpha v
or alpha IIb resulted in variants expressing alpha v beta 3, as in the
wild type, or alpha IIb beta 3. Both variants were able to associate
with thrombi and to arrest during blood flow, Therefore, beta 3 integr
in-mediated binding to activated platelets represents an efficient mec
hanism for melanoma cell arrest under flow, and this may contribute to
the role of platelets in hematogenous metastasis.