Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 66, Issue 1, Pages 79-87Publisher
SPRINGER
DOI: 10.1007/s00280-009-1136-0
Keywords
Melanoma; Angiogenesis; AT1 receptors; Angiotensin II; Losartan
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [1998/14247-6, 2006/60200-0]
- Conselho Nacional de Desenvolvimento Cientifico and Ministerio da Sa de/DECIT [401030/05-9, 152083/06-5]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [98/14247-6] Funding Source: FAPESP
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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.
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