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@ARTICLE{Costa:143436,
      author       = {B. M. Costa$^*$ and T. Eisemann$^*$ and J. Strelau and I.
                      Spaan$^*$ and A. Korshunov$^*$ and H.-K. Liu$^*$ and P.
                      Bugert and P. Angel$^*$ and H. Peterziel$^*$},
      title        = {{I}ntratumoral platelet aggregate formation in a murine
                      preclinical glioma model depends on podoplanin expression on
                      tumor cells.},
      journal      = {Blood advances},
      volume       = {3},
      number       = {7},
      issn         = {2473-9537},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2019-01024},
      pages        = {1092 - 1102},
      year         = {2019},
      note         = {DKFZ-ZMBH Alliance},
      abstract     = {Binding of the sialomucin-like transmembrane glycoprotein
                      podoplanin (PDPN) to the platelet receptor C-type
                      lectin-like receptor 2 induces platelet activation and
                      aggregation. In human high-grade gliomas, PDPN is highly
                      expressed both in tumor cells and in tumor-associated
                      astrocytes. In glioma patients, high expression of PDPN is
                      associated with worse prognosis and has been shown to
                      correlate with intratumoral platelet aggregation and an
                      increased risk of venous thromboembolism (VTE). To
                      functionally assess the role of PDPN in platelet aggregation
                      in vivo, we established a syngeneic orthotopic murine glioma
                      model in C57/Bl6 mice, based on transplantation of p53- and
                      Pten-deficient neural stem cells. This model is
                      characterized by the presence of intratumoral platelet
                      aggregates and by the upregulation of PDPN both in glioma
                      cells and in astrocytes, reflecting the characteristics of
                      human gliomas. Deletion of PDPN either in tumor cells or in
                      astrocytes resulted in glioma formation with similar
                      penetrance and grade compared with control mice.
                      Importantly, only the lack of PDPN in tumor cells, but not
                      in astrocytes, caused a significant reduction in
                      intratumoral platelet aggregates, whereas in vitro, both
                      cell types have similar platelet aggregation-inducing
                      capacities. Our results demonstrate a causative link between
                      PDPN and platelet aggregation in gliomas and pinpoint the
                      tumor cells as the major players in PDPN-induced platelet
                      aggregation. Our data indicate that blocking PDPN
                      specifically on tumor cells could represent a novel strategy
                      to prevent platelet aggregation and thereby reduce the risk
                      of VTE in glioma patients.},
      cin          = {A100 / B300 / A240},
      ddc          = {610},
      cid          = {I:(DE-He78)A100-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)A240-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30948364},
      pmc          = {pmc:PMC6457221},
      doi          = {10.1182/bloodadvances.2018015966},
      url          = {https://inrepo02.dkfz.de/record/143436},
}