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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and attenuates growth of murine melanoma

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Otake, Andreia Hanada [1, 2] ; Mattar, Ana Lucia [3] ; Freitas, Helano Carioca [1, 2] ; Longo Machado, Camila Maria [1, 2] ; Nonogaki, Suely [4] ; Fujihara, Clarice Kazue [3] ; Zatz, Roberto [3] ; Chammas, Roger [1, 2]
Total Authors: 8
[1] Univ Sao Paulo, Fac Med, Dept Radiol, Lab Oncol Expt LIM 24, BR-01246903 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, BR-01246903 Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med, Dept Clin Med, Lab Fisiopatol Renal LIM 16, BR-01246903 Sao Paulo - Brazil
[4] Inst Adolfo Lutz Registro, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Cancer Chemotherapy and Pharmacology; v. 66, n. 1, p. 79-87, MAY 2010.
Web of Science Citations: 37

Purpose We evaluated the involvement of angiotensin II (AngII)-dependent pathways in melanoma growth, through the pharmacological blockage of AT1 receptor by the antihypertensive 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 tumorassociated 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. (AU)

FAPESP's process: 98/14247-6 - Center for Research on Cell-Based Therapy
Grantee:Marco Antonio Zago
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC