• Medientyp: E-Artikel
  • Titel: Flt-1 Signaling in Macrophages Promotes Glioma Growth In vivo
  • Beteiligte: Kerber, Mark; Reiss, Yvonne; Wickersheim, Anke; Jugold, Manfred; Kiessling, Fabian; Heil, Matthias; Tchaikovski, Vadim; Waltenberger, Johannes; Shibuya, Masabumi; Plate, Karl H.; Machein, Marcia Regina
  • Erschienen: American Association for Cancer Research (AACR), 2008
  • Erschienen in: Cancer Research
  • Umfang: 7342-7351
  • Sprache: Englisch
  • DOI: 10.1158/0008-5472.can-07-6241
  • ISSN: 0008-5472; 1538-7445
  • Schlagwörter: Cancer Research ; Oncology
  • Zusammenfassung: <jats:title>Abstract</jats:title> <jats:p>Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and PlGF, is a positive regulator of angiogenesis in the context of tumor growth and metastasis. However, the molecular basis of its action is still not clear. Besides endothelial cells, Flt-1 is also expressed by other different cell types, including myeloid hematopoeitic cells (monocytes and macrophages). To examine the functions of Flt-1 expressed by bone marrow–derived myeloid cells in supporting tumor growth and angiogenesis, Flt-1 tyrosine kinase–deficient (Flt-1 TK−/−) bone marrow cells were transplanted into lethally irradiated syngeneic recipients. After hematopoietic reconstitution, we orthotopically implanted syngeneic wild-type glioma cells or glioma cells overexpressing either VEGF164 or PlGF-2. Loss of Flt-1 signaling in bone marrow–derived myeloid cells led to a significant decrease in tumor volume and vascularization in gliomas. VEGF but not PlGF overexpressed by glioma cells restored the tumor growth rate in Flt-1 TK−/− bone marrow chimera. VEGF and PlGF overexpression by tumor cells induced an accumulation of bone marrow–derived myeloid cells into tumor tissue. This infiltration was decreased in tumors grown in Flt-1 TK−/− bone marrow chimeras. When investigating chemokines and growth factors involved in myeloid cell recruitment, we determined elevated SDF-1/CXCL12 levels in VEGF- and PlGF-overexpressing tumors. Collectively, these results suggest that Flt-1 signaling in myeloid cells is essential to amplify the angiogenic response and to promote glioma growth. [Cancer Res 2008;68(18):7342–51]</jats:p>
  • Beschreibung: <jats:title>Abstract</jats:title>
    <jats:p>Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and PlGF, is a positive regulator of angiogenesis in the context of tumor growth and metastasis. However, the molecular basis of its action is still not clear. Besides endothelial cells, Flt-1 is also expressed by other different cell types, including myeloid hematopoeitic cells (monocytes and macrophages). To examine the functions of Flt-1 expressed by bone marrow–derived myeloid cells in supporting tumor growth and angiogenesis, Flt-1 tyrosine kinase–deficient (Flt-1 TK−/−) bone marrow cells were transplanted into lethally irradiated syngeneic recipients. After hematopoietic reconstitution, we orthotopically implanted syngeneic wild-type glioma cells or glioma cells overexpressing either VEGF164 or PlGF-2. Loss of Flt-1 signaling in bone marrow–derived myeloid cells led to a significant decrease in tumor volume and vascularization in gliomas. VEGF but not PlGF overexpressed by glioma cells restored the tumor growth rate in Flt-1 TK−/− bone marrow chimera. VEGF and PlGF overexpression by tumor cells induced an accumulation of bone marrow–derived myeloid cells into tumor tissue. This infiltration was decreased in tumors grown in Flt-1 TK−/− bone marrow chimeras. When investigating chemokines and growth factors involved in myeloid cell recruitment, we determined elevated SDF-1/CXCL12 levels in VEGF- and PlGF-overexpressing tumors. Collectively, these results suggest that Flt-1 signaling in myeloid cells is essential to amplify the angiogenic response and to promote glioma growth. [Cancer Res 2008;68(18):7342–51]</jats:p>
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  • Zugangsstatus: Freier Zugang