title: Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and attenuates growth of murine melanoma.
abstract: OBJECTIVE
  We evaluated the involvement of angiotensin II (AngII)-dependent pathways in melanoma growth, through the pharmacological blockage of AT1 receptor by the anti-hypertensive drug losartan (LOS).
  
  
  RESULTS
  We showed immunolabeling for both AngII and the AT1 receptor within the human melanoma microenvironment. Like human melanomas, we showed that murine melanomas also express the AT1 receptor. Growth of murine melanoma, both locally and at distant sites, was limited in mice treated with LOS. The reduction in tumor growth was accompanied by a twofold decrease in tumor-associated microvessel density and by a decrease in CD31 mRNA levels. While no differences were found in the VEGF expression levels in tumors from treated animals, reduction in the expression of the VEGFR1 (Flt-1) at the mRNA and protein levels was observed. We also showed downregulation of mRNA levels of both Flt-4 and its ligand, VEGF-C.
  
  
  CONCLUSIONS
  Together, these results show that blockage of AT1 receptor signaling may be a promising anti-tumor strategy, interfering with angiogenesis by decreasing the expression of angiogenic factor receptors.
authors.affiliation: Laboratório de Oncologia Experimental (LIM-24), Departamento de Radiologia e Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo, 455 room 4112/4122, São Paulo, Brazil.
authors.forename: Andréia Hanada
authors.initials: AH
authors.lastname: Otake
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Mattar
authors.forename: Helano Carioca
authors.initials: HC
authors.lastname: Freitas
authors.forename: Camila Maria Longo
authors.initials: CM
authors.lastname: Machado
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.forename: Clarice Kazue
authors.initials: CK
authors.lastname: Fujihara
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D042501:Angiogenic Proteins; D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan