title: Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 integrin mediates interaction of melanoma cells with platelets: a connection to hematogenous metastasis.
abstract: A mutual relationship exists between metastasizing tumor cells and components of the coagulation cascade. The exact mechanisms as to how platelets influence blood-borne metastasis, however, remain poorly understood. Here, we used murine B16 melanoma cells to observe functional aspects of how platelets contribute to the process of hematogenous metastasis. We found that platelets interfere with a distinct step of the metastasis cascade, as they promote adhesion of melanoma cells to the endothelium in vitro under shear conditions. Constitutively active platelet receptor GPIIb/IIIa (integrin αIIbβ3) expressed on Chinese hamster ovary cells promoted melanoma cell adhesion in the presence of fibrinogen, whereas blocking antibodies to aνβ3 integrin on melanoma cells or to GPIIb/IIIa significantly reduced melanoma cell adhesion to platelets. Furthermore, using intravital microscopy, we observed functional platelet-melanoma cell interactions, as platelet depletion resulted in significantly reduced melanoma cell adhesion to the injured vascular wall in vivo. Using a mouse model of hematogenous metastasis to the lung, we observed decreased metastasis of B16 melanoma cells to the lung by treatment with a mAb blocking the aν subunit of aνβ3 integrin. This effect was significantly reduced when platelets were depleted in vivo. Thus, the engagement of GPIIb/IIIa with aνβ3 integrin interaction mediates tumor cell-platelet interactions and highlights how this interaction is involved in hematogenous tumor metastasis.
authors.affiliation: Department of Dermatology, University Hospital, Ruprecht-Karls University Heidelberg, 69115 Heidelberg, Germany. anke.lonsdorf@med.uni-heidelberg.de
authors.forename: Anke S
authors.initials: AS
authors.lastname: Lonsdorf
authors.forename: Björn F
authors.initials: BF
authors.lastname: Krämer
authors.forename: Manuela
authors.initials: M
authors.lastname: Fahrleitner
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Stephan
authors.initials: S
authors.lastname: Gnerlich
authors.forename: Sabine
authors.initials: S
authors.lastname: Ring
authors.forename: Sarah
authors.initials: S
authors.lastname: Gehring
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kruhlak
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Enk
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
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