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@ARTICLE{Buhl:143210,
      author       = {J. L. Buhl$^*$ and F. Selt$^*$ and T. Hielscher$^*$ and R.
                      Guiho and J. Ecker$^*$ and F. Sahm$^*$ and J. Ridinger$^*$
                      and D. Riehl$^*$ and D. Usta$^*$ and B. Ismer$^*$ and A. C.
                      Sommerkamp$^*$ and J. P. Martinez-Barbera and A. K.
                      Wefers$^*$ and M. Remke$^*$ and D. Picard$^*$ and S.
                      Pusch$^*$ and J. Gronych$^*$ and I. Oehme$^*$ and C. M. van
                      Tilburg$^*$ and M. Kool$^*$ and D. Kuhn$^*$ and D.
                      Capper$^*$ and A. von Deimling$^*$ and M. U. Schuhmann and
                      C. Herold-Mende and A. Korshunov$^*$ and T. Brummer$^*$ and
                      S. Pfister$^*$ and D. Jones$^*$ and O. Witt$^*$ and T.
                      Milde$^*$},
      title        = {{T}he {S}enescence-associated {S}ecretory {P}henotype
                      {M}ediates {O}ncogene-induced {S}enescence in {P}ediatric
                      {P}ilocytic {A}strocytoma.},
      journal      = {Clinical cancer research},
      volume       = {25},
      number       = {6},
      issn         = {1557-3265},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2019-00809},
      pages        = {1851 - 1866},
      year         = {2019},
      abstract     = {Pilocytic astrocytoma is the most common childhood brain
                      tumor, characterized by constitutive MAPK activation. MAPK
                      signaling induces oncogene-induced senescence (OIS), which
                      may cause unpredictable growth behavior of pilocytic
                      astrocytomas. The senescence-associated secretory phenotype
                      (SASP) has been shown to regulate OIS, but its role in
                      pilocytic astrocytoma remains unknown.Experimental Design:
                      The patient-derived pilocytic astrocytoma cell culture
                      model, DKFZ-BT66, was used to demonstrate presence of the
                      SASP and analyze its impact on OIS in pilocytic astrocytoma.
                      The model allows for doxycycline-inducible switching between
                      proliferation and OIS. Both states were studied using gene
                      expression profiling (GEP), Western blot, ELISA, and cell
                      viability testing. Primary pilocytic astrocytoma tumors were
                      analyzed by GEP and multiplex assay.SASP factors were
                      upregulated in primary human and murine pilocytic
                      astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned
                      medium induced growth arrest of proliferating pilocytic
                      astrocytoma cells. The SASP factors IL1B and IL6 were
                      upregulated in primary pilocytic astrocytoma, and both
                      pathways were regulated during OIS in DKFZ-BT66. Stimulation
                      with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells
                      and induced the SASP. Anti-inflammatory treatment with
                      dexamethasone induced regrowth of senescent cells and
                      inhibited the SASP. Senescent DKFZ-BT66 cells responded to
                      senolytic BCL2 inhibitors. High IL1B and SASP expression in
                      pilocytic astrocytoma tumors was associated with favorable
                      progression-free survival.We provide evidence for the SASP
                      regulating OIS in pediatric pilocytic astrocytoma, with IL1B
                      as a relevant mediator. SASP expression could enable
                      prediction of progression in patients with pilocytic
                      astrocytoma. Further investigation of the SASP driving the
                      unpredictable growth of pilocytic astrocytomas, and its
                      possible therapeutic application, is warranted.},
      cin          = {B310 / C060 / B300 / B062 / L401 / B060 / B360 / L101 /
                      L601 / L201},
      ddc          = {610},
      cid          = {I:(DE-He78)B310-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)L401-20160331 / I:(DE-He78)B060-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L601-20160331 / I:(DE-He78)L201-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30530705},
      doi          = {10.1158/1078-0432.CCR-18-1965},
      url          = {https://inrepo02.dkfz.de/record/143210},
}