title: Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis.
abstract: 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.
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Echtler
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Konrad
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.affiliation: Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hofmaier
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Plenagl
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stark
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Czermak
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Anca
authors.initials: A
authors.lastname: Tirniceriu
authors.affiliation: Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.|Chirurgische Klinik, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eichhorn
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Enders
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.|Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D008175:Lung Neoplasms / Q000097:blood / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008833:Microcirculation; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism*
chemical_list: D040201:Platelet Membrane Glycoprotein IIb