Regulation of platelet-derived growth factor signaling by activated p21Ras

Ll, Stice; Vaziri, Cyrus; Dv, Faller

doi:10.2741/stice

Cited by 14 publications

(4 citation statements)

References 13 publications

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“…A possible explanation could be the role of PDGFR-β in tissue growth and repair. Our results support the findings of Stice et al [36], who postulated that PDGFR-β is suppressed by oncogenes such as p21ras. It is most likely that in the absence of a tumor burden, after debulking surgery and after chemotherapy, PDGFR-β acts as it would under benign conditions, and is increased due to pericyte recruitment to capillaries, the development of smooth muscle cells in vessels, etc.…”

Section: Discussionsupporting

confidence: 83%

Platelet-Derived Growth Factor Receptor Beta Serum Concentrations during First-Line Therapy in Ovarian Cancer

Mathey¹,

Graeser²,

Eulenburg

et al. 2013

Oncology

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Objectives: Angiogenesis plays an important role in ovarian cancer. The interaction of platelet-derived growth factor receptor-beta (PDGFR-β) with vascular endothelial growth factor (VEGF) in the process of angiogenesis may represent an essential feature in the progression of the disease. Methods: Patients with epithelial ovarian cancer, who underwent primary surgery and platinum-based first-line chemotherapy, were included. A total of 133 serum samples from 39 patients were analyzed. Samples were prospectively collected at 4 time points: (1) before surgery, (2) after surgery and before chemotherapy, (3) during chemotherapy and (4) after chemotherapy. Serum PDGFR-β was quantified by ELISA. We analyzed the correlation of serum levels to chemotherapy response, progression-free and overall survival (PFS and OS) and the serum markers CA-125 and VEGF-165. Results: Serum concentration of PDGFR-β ranged between 4 and 72 ng/ml and increased significantly during first-line chemotherapy (p = 0.019). PDGFR-β serum concentrations showed an inverse correlation with CA-125 and VEGF-165 after chemotherapy (r = -0.495, p = 0.003 and r = -0.345, p = 0.04, respectively). Increased PDGFR-β serum levels after chemotherapy were significantly correlated with better PFS (p = 0.026) and OS (p = 0.013) in a univariate analysis. Conclusion: PDGFR-β might be a useful biomarker in terms of prognosis and could be important as antiangiogenic agents become a component of standard treatment in ovarian cancer.

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Section: Discussionsupporting

confidence: 83%

Platelet-Derived Growth Factor Receptor Beta Serum Concentrations during First-Line Therapy in Ovarian Cancer

Mathey¹,

Graeser²,

Eulenburg

et al. 2013

Oncology

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“…1 and 6). The adapter protein p52-ShcA has been reported to influence proliferation in smooth muscle cells (42) and epithelial cells (47). Also, p52/46 ShcA-induced Ras activation has been linked to growth and proliferation (30).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of interleukin-2-induced mucosal homeostasis

Mishra

Waters

Kumar

2012

American Journal of Physiology-Cell Physiology

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“…Two separate mechanisms are taken into account for defective PDGFRβ signaling: transcriptional down-regulation of PDGFRβ expression and inhibition of ligand-induced PDGFRβ by a factor of the cell membrane of p21Ras-expressing fibroblasts [21]. Reversion of the cell phenotype results in the recovery of the PDGFRβ kinase activity.…”

Section: Pdgf and Pdgfr Familymentioning

confidence: 99%

Platelet-Derived Growth Factor (PDGF)/PDGF Receptors (PDGFR) Axis as Target for Antitumor and Antiangiogenic Therapy

2010

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Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF), fibroblast growth factor (FGF)-2 or platelet-derived growth factors (PDGF). From these, VEGF and FGF-2 were extensively investigated and it was shown that they significantly contribute to the induction and progression of angiogenesis. A lot of evidence has been accumulated in last 10 years that supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-β in angiogenesis has been demonstrated by gene targeting experiments, and their expression correlates with increased vascularity and maturation of the vascular wall. PDGF and their receptors were identified in a large variety of human tumor cells. In experimental models it was shown that inhibition of PDGF reduces interstitial fluid pressure in tumors and enhances the effect of chemotherapy. PDGFR have been involved in the cardiovascular development and their loss leads to a disruption in yolk sac blood vessels development. PDGFRβ expression by pericytes is necessary for their recruitment and integration in the wall of tumor vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR. Based on these data, it was suggested the potential benefit of targeting PDGFR in the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated angiogenesis are not fully understood, but it was shown that tyrosine kinase inhibitors reduce tumor growth and angiogenesis in experimental xenograft models, and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo effects of PDGFR inhibitors are more complex, based on the cross-talk with other angiogenic factors. In this review, we summarize data regarding the mechanisms and significance of PDGF/PDGFR expression in normal conditions and tumors, focusing on this axis as a potential target for antitumor and antiangiogenic therapy.

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Regulation of platelet-derived growth factor signaling by activated p21Ras

Cited by 14 publications

References 13 publications

Platelet-Derived Growth Factor Receptor Beta Serum Concentrations during First-Line Therapy in Ovarian Cancer

Platelet-Derived Growth Factor Receptor Beta Serum Concentrations during First-Line Therapy in Ovarian Cancer

Molecular mechanism of interleukin-2-induced mucosal homeostasis

Platelet-Derived Growth Factor (PDGF)/PDGF Receptors (PDGFR) Axis as Target for Antitumor and Antiangiogenic Therapy

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