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Kubacka, Urszula; Nagengast, Wouter B.; Kruizinga, Roeliene C.; Lub-deHooge, Marjolijn N.; Gietema, Jourik A.; Oosting, Sjoukje F.; Timmer-Boscha, Hetty; Hospers, Geke A.; den Dunnen, Wilfred F.; de Vries, Elisabeth G.; Huls, Gerwin; Walenkamp, Annemiek M.

Abstract 380: Sunitinib treatment induces up-regulation of CXCR4

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  • Media type: E-Article
  • Title: Abstract 380: Sunitinib treatment induces up-regulation of CXCR4
  • Contributor: Kubacka, Urszula; Nagengast, Wouter B.; Kruizinga, Roeliene C.; Lub-deHooge, Marjolijn N.; Gietema, Jourik A.; Oosting, Sjoukje F.; Timmer-Boscha, Hetty; Hospers, Geke A.; den Dunnen, Wilfred F.; de Vries, Elisabeth G.; Huls, Gerwin; Walenkamp, Annemiek M.
  • imprint: American Association for Cancer Research (AACR), 2010
  • Published in: Cancer Research
  • Language: English
  • DOI: 10.1158/1538-7445.am10-380
  • ISSN: 0008-5472; 1538-7445
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>Background: Chemokine receptors expressed on solid tumor cells and their corresponding ligands are an example of a network which is used by these cells to interact with their microenvironment to sustain survival, proliferation, invasive growth, angiogenesis, and to promote organ-specific localization of distant metastases. Indeed, CXCR4/CXCL12 signaling can induce angiogenesis and progression of tumors, for example by increasing the expression of vascular endothelial growth factor (VEGF). Inversely, it is hypothesized that anti-angiogenic treatment increases the expression of CXCR4/CXCL12 which could explain the in preclinical models observed invasive growth characteristics of tumors.</jats:p> <jats:p>Methods: A human A2780 ovarian xenograft mouse model was used. When the tumor was established, mice were treated with vehicle or sunitinib (60 mg/kg i.p.) daily for 2 weeks. CXCR4 expression was assessed by immunohistochemistry at baseline and after 1 and 2 weeks of treatment and compared with markers like HIF1α, VEGF, Ki67, VEGFR2, mean vessel density (MVD) and blood vessel diameter. In addition human plasma VEGF levels were analyzed.</jats:p> <jats:p>Results: Moderate cell membrane CXCR4 expression was seen in untreated tumors. One week of sunitinib treatment resulted in decrease angiogenice markers and tumor proliferation (Ki67) in both the tumor center and rim. Two weeks of sunitinib treatment resulted in up regulation of CXCR4 with a 2.2 fold increase (P = 0.046) particularly in the tumor rim. This coincided with normalization of blood vessel diameters, intense VEGF staining and increased tumor proliferation (Ki67) to baseline levels in the tumor rim. In contrast, an increase of HIF1α (P = 0.017) and decrease of angiogenic markers like VEGFR2 (P = 0.019) and MVD (P = 0.016) was still observed in the tumor center.</jats:p> <jats:p>Conclusion: This study shows that anti-angiogenic treatment with sunitinib up regulates CXCR4 expression, mainly in the rim of the tumor. CXCR4 is a potential target to block anti-angiogenic induced invasive growth/metastasis.</jats:p> <jats:p>Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.</jats:p> <jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 380.</jats:p>
  • Access State: Open Access