INVESTIGADORES
COLUCCIO LESKOW Federico
artículos
Título:
Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer.
Autor/es:
FERRANDO M; GERRON G; ELGUERO B; GIUDICE J; SALLES A; LESKOW FC; JARES-ERIJMAN EA; COLOMBO L; MEISS R; NAVONE N; DE SIERVI A; VAZQUEZ E
Revista:
ANGIOGENESIS
Editorial:
SPRINGER
Referencias:
Lugar: Nueva York; Año: 2011 vol. 14 p. 467 - 479
ISSN:
0969-6970
Resumen:
Prostate cancer (PCa) is the second leading cause of cancer-associated
death in men. Once a tumor is established it may attain further
characteristics via mutations or hypoxia, which stimulate new blood
vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and
inflammatory diseases that may predispose to cancer. Heme oxygenase-1
(HO-1) counteracts oxidative and inflammatory damage and was previously
reported to play a key role in prostate carcinogenesis. To gain insight
into the anti-tumoral properties of HO-1, we investigated its capability
to modulate PCa associated-angiogenesis. In the present study, we
identified in PC3 cells a set of inflammatory and pro-angiogenic genes
down-regulated in response to HO-1 overexpression, in particular VEGFA,
VEGFC, HIF1α and α5β1 integrin. Our results indicated that HO-1
counteracts oxidative imbalance reducing ROS levels. An in vivo
angiogenic assay showed that intradermal inoculation of PC3 cells stable
transfected with HO-1 (PC3HO-1) generated tumours less vascularised
than controls, with decreased microvessel density and reduced CD34 and
MMP9 positive staining. Interestingly, longer term grown PC3HO-1
xenografts displayed reduced neovascularization with the subsequent
down-regulation of VEGFR2 expression. Additionally, HO-1 repressed
nuclear factor κB (NF-κB)-mediated transcription from an NF-κB
responsive luciferase reporter construct, which strongly suggests that
HO-1 may regulate angiogenesis through this pathway. Taken together,
these data supports a key role of HO-1 as a modulator of the angiogenic
switch in prostate carcinogenesis ascertaining it as a logical target
for intervention therapy.