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@ARTICLE{DAsti:119849,
      author       = {E. D'Asti and M. Kool$^*$ and S. Pfister$^*$ and J. Rak},
      title        = {{C}oagulation and angiogenic gene expression profiles are
                      defined by molecular subgroups of medulloblastoma: evidence
                      for growth factor-thrombin cross-talk.312},
      journal      = {Journal of thrombosis and haemostasis},
      volume       = {12},
      number       = {11},
      issn         = {1538-7933},
      address      = {Oxford},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2017-00444},
      pages        = {1838 - 1849},
      year         = {2014},
      abstract     = {The coagulation system becomes activated during progression
                      and therapy of high-grade brain tumors. Triggering tissue
                      factor (F3/TF) and thrombin receptors (F2R/PAR-1) may
                      influence the vascular tumor microenvironment and
                      angiogenesis irrespective of clinically apparent thrombosis.
                      These processes are poorly understood in medulloblastoma
                      (MB), in which diverse oncogenic pathways define at least
                      four molecular disease subtypes (WNT, SHH, Group 3 and Group
                      4). We asked whether there is a link between molecular
                      subtype and the network of vascular regulators expressed in
                      MB.Using R2 microarray analysis and visualization platform,
                      we mined MB datasets for differential expression of vascular
                      (coagulation and angiogenesis)-related genes, and explored
                      their link to known oncogenic drivers. We evaluated the
                      functional significance of this link in DAOY cells in vitro
                      following growth factor and thrombin stimulation.The
                      coagulome and angiome differ across MB subtypes. F3/TF and
                      F2R/PAR-1 mRNA expression are upregulated in SHH tumors and
                      correlate with higher levels of hepatocyte growth factor
                      receptor (MET). Cultured DAOY (MB) cells exhibit an
                      up-regulation of F3/TF and F2R/PAR-1 following combined SHH
                      and MET ligand (HGF) treatment. These factors cooperate with
                      thrombin, impacting the profile of vascular regulators,
                      including interleukin 1β (IL1B) and chondromodulin 1
                      (LECT1).Coagulation pathway sensors (F3/TF, F2R/PAR-1) are
                      expressed in MB in a subtype-specific manner, and may be
                      functionally linked to SHH and MET circuitry. Thus
                      coagulation system perturbations may elicit
                      subtype/context-specific changes in vascular and cellular
                      responses in MB.},
      keywords     = {Angiogenic Proteins (NLM Chemicals) / Hedgehog Proteins
                      (NLM Chemicals) / Intercellular Signaling Peptides and
                      Proteins (NLM Chemicals) / RNA, Messenger (NLM Chemicals) /
                      Receptor, PAR-1 (NLM Chemicals) / Hepatocyte Growth Factor
                      (NLM Chemicals) / Thromboplastin (NLM Chemicals) / MET
                      protein, human (NLM Chemicals) / Proto-Oncogene Proteins
                      c-met (NLM Chemicals) / Thrombin (NLM Chemicals)},
      cin          = {B062},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25163932},
      doi          = {10.1111/jth.12715},
      url          = {https://inrepo02.dkfz.de/record/119849},
}