title: Functional VEGF and VEGF receptors are expressed in human medulloblastomas.
abstract: Vascular endothelial growth factor (VEGF) is one of the key regulators of tumor neoangiogenesis. It acts through two types of high-affinity tyrosine kinase receptors (VEGF receptor-1 [VEGFR-1]/fms-related tyrosine kinase 1 [Flt-1] and VEGFR-2/kinase domain receptor [KDR]) expressed on endothelial cells. VEGFRs have also been detected on cancer cells, suggesting a possible autocrine effect of VEGF on their growth. We studied the expression of VEGF, VEGFR-1, and VEGFR-2 in human medulloblastoma cell lines (DAOY, D283Med, and D341Med) and investigated the possible autocrine mechanisms of VEGF on medulloblastoma cell proliferation. Reverse transcriptase PCR analysis showed the presence of VEGF and VEGFR mRNAs in all cell lines studied. Of the three VEGF isoforms, VEGF(121) and VEGF(189) were detected by Western blot analysis in all three medulloblastoma cell lines, whereas VEGF(165) was identified only in DAOY cells. Medulloblastoma cell lines expressed both VEGFR-1 and VEGFR-2. We also demonstrated expression of VEGF and its receptors in medulloblastoma tumor specimens. Exogenous VEGFR-2 inhibitor reduced the VEGF-dependent cell proliferation of DAOY and D283Med cells. In DAOY cells, VEGF(165) induced phosphorylation of VEGFR-2/KDR and of downstream proteins in the signal transduction pathway. These data suggest a possible autocrine role for VEGF in medulloblastoma growth. Targeting VEGF signaling may represent a new therapeutic option in the treatment of medulloblastoma.
authors: Department of Experimental Biomedical Sciences, Division of Hematology-Oncology, University-Hospital of Padua, Via Giustiniani 3, 35128 Padua, Italy.
authors: M Liliana
authors: ML
authors: Slongo
authors: Beatrice
authors: B
authors: Molena
authors: Anna Maria
authors: AM
authors: Brunati
authors: Martina
authors: M
authors: Frasson
authors: Marina
authors: M
authors: Gardiman
authors: Modesto
authors: M
authors: Carli
authors: Giorgio
authors: G
authors: Perilongo
authors: Angelo
authors: A
authors: Rosolen
authors: Maurizio
authors: M
authors: Onisto
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor
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