2004
DOI: 10.1161/01.res.0000126925.66005.39
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Essential Role of PDGFRα-p70S6K Signaling in Mesenchymal Cells During Therapeutic and Tumor Angiogenesis In Vivo

Abstract: Abstract-Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-␣ (PDGFR␣)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor… Show more

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Cited by 59 publications
(87 citation statements)
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“…We thus next focused on the role of VEGF-A/VPF and its potent autocrine upstream regulator, platelet-derived growth factor AA (PDGF-AA; refs. [29][30][31]. Of interest, accumulation of VEGF-A/VPF, but not of PDGF-AA, in MA was found (data not shown); therefore, elevated levels of VEGF-A/VPF might be due to the unregulated expression of VEGF-A/VPF from cancer cells.…”
Section: Discussionmentioning
confidence: 92%
“…We thus next focused on the role of VEGF-A/VPF and its potent autocrine upstream regulator, platelet-derived growth factor AA (PDGF-AA; refs. [29][30][31]. Of interest, accumulation of VEGF-A/VPF, but not of PDGF-AA, in MA was found (data not shown); therefore, elevated levels of VEGF-A/VPF might be due to the unregulated expression of VEGF-A/VPF from cancer cells.…”
Section: Discussionmentioning
confidence: 92%
“…Rapamycin also targets vascular mesenchymal cells (pericytes, smooth muscle cells, and adventitial fibroblasts) inhibiting sustained VEGF and hepatocyte growth factor expression via silencing of the platelet-derived growth factor receptor-a/S6 kinase 1 (S6K1) pathway. As rapamycin showed only a minimal effect on hypoxia-related expression of VEGF in culture, these results suggest targeting of the host vasculature rather than tumor itself in vivo (12,13).…”
Section: Introductionmentioning
confidence: 79%
“…A possible target cell for PDGF-A is the smooth muscle cell [Edelberg et al, 2002;Machens et al, 2002;Tsutsumi et al, 2004]. PDGF has a potent mitogenic effect in cells of mesenchymal origin.…”
Section: Discussionmentioning
confidence: 99%