Data from: Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis

Platelets modulate the process of cancer metastasis. However, current
knowledge on the direct interaction of platelets and tumor cells is mostly
based on findings obtained in vitro. We addressed the role of the platelet
fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental
melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were
injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT)
mice. Acute accumulation of tumor cells in the pulmonary vasculature was
assessed in real-time by confocal videofluorescence microscopy. Arrest of
tumor cells was dramatically reduced in GPIIb-/- mice as compared to WT.
Importantly, we found that mainly multicellular aggregates accumulated in
the pulmonary circulation of WT, instead B16-D5 aggregates were
significantly smaller in GPIIb-/- mice. While pulmonary arrest of melanoma
was clearly dependent on GPIIb in this early phase of metastasis, we also
addressed tumor progression 10 days after injection. Inversely, and
unexpectedly, we found that melanoma metastasis was now increased in
GPIIb-/- mice. In contrast, GPIIb did not regulate local melanoma
proliferation in a subcutaneous tumor model. Our data suggest that the
platelet fibrinogen receptor has a differential role in the modulation of
hematogenic melanoma metastasis. While platelets clearly support early
steps in pulmonary metastasis via GPIIb-dependent formation of
platelet-tumor-aggregates, at a later stage its absence is associated with
an accelerated development of melanoma metastases.