title: Vascular endothelial growth factor as a biomarker for endostatin gene therapy.
abstract: Renal cell carcinoma (RCC) is characterized by high vascular endothelial growth factor (VEGF) production and, consequently, excessive angiogenesis. Several strategies have been developed to target angiogenesis as a method for treating metastatic RCC (mRCC). Endostatin (ES) is a C-terminal fragment of collagen XVIII that has antiangiogenic activity. The aim of this study was to investigate the predictive value of circulating VEGF-A in a murine model of mRCC after ES gene therapy. ES therapy did not affect the levels of collagen XVIII/ES or ES in the tissue. The circulating level of ES was increased in the control and ES-treated groups (normal vs. control, P<0.05 and ES-treated vs. control, P<0.001), and the intratumoral vessels were significantly decreased (ES-treated vs. control, P<0.05). ES therapy decreased the VEGF mRNA levels. The tissue and circulating levels of VEGF in the control group were significantly higher than normal (P<0.01 and P<0.05, respectively). Treatment with ES significantly reduced the VEGF concentrations in both compartments (P<0.001 for tissue and P<0.05 for plasma). Our findings indicate that in addition to the directly targeted tumor vessels, ES exerts its antitumor effect by down-regulating VEGF gene expression in renal tumor cells. Additionally, our findings point to the predictive value of VEGF for ES therapy.
authors.affiliation: Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Marina Souza
authors.initials: MS
authors.lastname: Braga
authors.forename: Thiago Lauro
authors.initials: TL
authors.lastname: Turaça
authors.forename: Karen
authors.initials: K
authors.lastname: Foguer
authors.forename: Karen Cristina Barbosa
authors.initials: KC
authors.lastname: Chaves
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Bellini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D043170:Collagen Type XVIII / Q000235:genetics; D043169:Endostatins / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D043170:Collagen Type XVIII; D043169:Endostatins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: Biomarker; Endostatin; Orthotopic metastatic model; RCC; VEGF