title: Fibronectin expression is decreased in metastatic renal cell carcinoma following endostatin gene therapy.
abstract: Tumor cells induce the disruption of homeostasis between cellular and extracellular compartments to favor tumor progression. The expression of fibronectin (FN), a matrix glycoprotein, is increased in several carcinoma cell types, including renal cell carcinoma (RCC). RCC are highly vascularized tumors and are often amenable to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the modulation of FN gene expression by ES gene therapy in a murine metastatic renal cell carcinoma (mRCC) model. Balb/C mice bearing Renca cells were treated with NIH/3T3-LXSN cells or NIH/3T3-LendSN cells. At the end of the experiment, the ES serum levels were measured, and the FN gene expression was assessed using real-time PCR. The tissue FN was evaluated by western blotting and by immunofluorescence analysis. The ES serum levels in treated mice were higher than those in the control group (P<0.05). ES treatment led to significant decreases at the FN mRNA (P<0.001) and protein levels (P<0.01). Here, we demonstrate the ES antitumor effect that is mediated by down-regulation of FN expression in mRCC.
authors.affiliation: Nephrology Division, Medicine Department, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Karen Cristina Barbosa
authors.initials: KC
authors.lastname: Chaves
authors.forename: Lauro Thiago
authors.initials: LT
authors.lastname: Turaça
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Gregory
authors.initials: G
authors.lastname: Mennecier
authors.forename: Maria Lucia Zaidan
authors.initials: ML
authors.lastname: Dagli
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: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D002999:Clone Cells; D015536:Down-Regulation; D043169:Endostatins / Q000097:blood / Q000235:genetics* / Q000627:therapeutic use*; D005353:Fibronectins / Q000378:metabolism*; D015316:Genetic Therapy; D007680:Kidney Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood / Q000378:metabolism
chemical_list: D043169:Endostatins; D005353:Fibronectins; D012333:RNA, Messenger; D011994:Recombinant Proteins