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@ARTICLE{AbdulPari:154531,
      author       = {A. A. Abdul Pari$^*$ and M. Singhal$^*$ and C. Hübers$^*$
                      and C. Mogler and B. Schieb$^*$ and A. Gampp$^*$ and N.
                      Gengenbacher$^*$ and L. E. Reynolds and D. Terhardt$^*$ and
                      C. Géraud and J. Utikal$^*$ and M. Thomas and S. Goerdt and
                      K. M. Hodivala-Dilke and H. Augustin$^*$ and M. Felcht},
      title        = {{T}umor cell-derived {A}ngiopoietin-2 promotes metastasis
                      in melanoma.},
      journal      = {Cancer research},
      volume       = {80},
      number       = {12},
      issn         = {1538-7445},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2020-00852},
      pages        = {2586-2598},
      year         = {2020},
      note         = {DKFZ-ZMBH Alliance2020 Jun
                      15;80(12):2586-2598#EA:A190#LA:A190#},
      abstract     = {The Angiopoietin (Angpt)-TIE signaling pathway controls
                      vascular maturation and maintains the quiescent phenotype of
                      resting vasculature. The contextual agonistic and
                      antagonistic Tie2 ligand ANGPT2 is believed to be
                      exclusively produced by endothelial cells, disrupting
                      constitutive ANGPT1-TIE2 signaling to destabilize the
                      microvasculature during pathological disorders like
                      inflammation and cancer. However, scattered reports have
                      also portrayed tumor cells as a source of ANGPT2. Employing
                      in situ hybridization-based detection of ANGPT2, we found
                      strong tumor cell expression of ANGPT2 in a subset of
                      melanoma patients. Comparative analysis of biopsies revealed
                      a higher fraction of ANGPT2-expressing tumor cells in
                      metastatic versus primary sites. Tumor cell-expressed Angpt2
                      was dispensable for primary tumor growth, yet in-depth
                      analysis of primary tumors revealed enhanced intratumoral
                      necrosis upon silencing of tumor cell Angpt2 expression in
                      the absence of significant immune and vascular alterations.
                      Global transcriptional profiling of Angpt2-deficient tumor
                      cells identified perturbations in redox homeostasis and an
                      increased response to cellular oxidative stress.
                      Ultrastructural analyses illustrated a significant increase
                      of dysfunctional mitochondria in Angpt2-silenced tumor
                      cells, thereby resulting in enhanced ROS production and
                      downstream MAPK stress signaling. Functionally, enhanced ROS
                      in Angpt2-silenced tumor cells reduced colonization
                      potential in vitro and in vivo. Taken together, these
                      findings uncover the hitherto unappreciated role of tumor
                      cell-expressed ANGPT2 as an autocrine positive regulator of
                      metastatic colonization and validate ANGPT2 as a therapeutic
                      target for a well-defined subset of melanoma patients.},
      cin          = {A190 / A370 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)A190-20160331 / I:(DE-He78)A370-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32303578},
      doi          = {10.1158/0008-5472.CAN-19-2660},
      url          = {https://inrepo02.dkfz.de/record/154531},
}