The Effects of Platelet-Derived Growth Factor and Receptor on Normal and Neoplastic Human Ovarian Surface Epithelium

Dabrow, Michael; Francesco, Michelle; McBrearty, Francis X.; Caradonna, Salvatore J.

doi:10.1006/gyno.1998.5121

Cited by 90 publications

(43 citation statements)

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“…Using this as a reference, 12% of serous ovarian carcinomas showed decreased and 13% increased PDGFRA expression. In previous reports, PDGFRA immunopositivity has varied from 5 to 100% of ovarian carcinomas (Henriksen et al, 1993;Dabrow et al, 1998;Apte et al, 2004a;Matei et al, 2004). Little is known about its associations with clinical para meters.…”

Section: Discussionmentioning

confidence: 99%

“…This has raised hopes that some carcinomas could be treated with imatinib mesylate. In ovarian carcinomas, the reported frequency of KIT and PDGFRA expression has been highly variable, and little is known about their molecular background and association with clinical parameters (Henriksen et al, 1993;Inoue et al, 1994;Arber et al, 1998;Dabrow et al, 1998;Parrott et al, 2000;Tonary et al, 2000;Schmandt et al, 2003;Singer et al, 2003;Apte et al, 2004a;Matei et al, 2004). GISTs with KIT mutation, particularly in exon 11, show a clearly better response to imatinib therapy as compared to tumours with no mutation, suggesting that detection of gain-of-function mutation and not solely KIT expression should be a requirement for the treatment (Heinrich et al, 2003).…”

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confidence: 99%

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Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian carcinoma

et al. 2004

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KIT and PDGFRA are receptor tyrosine kinases that can be specifically inactivated by small-molecule tyrosine kinase inhibitors, notably imatinib mesylate. In ovarian carcinoma, expression of KIT and PDGFRA protein has been documented, but the frequency and the molecular background of expression are poorly known. We analysed the expression of KIT and PDGFRA by immunohistochemistry in 522 serous ovarian carcinomas, and mutations of KIT and PDGFRA by denaturing high-performance liquid chromatographyin 125 and 187 serous ovarian carcinomas, respectively. No mutations of KIT or PDGFRA were detected. KIT expression was detected in 12% of carcinomas: low expression in 10% and high expression in 2% of cases. Using normal serous epithelium as a reference, decreased PDGFRA expression was detected in 12% and increased expression in 13% of carcinomas. Both KIT and PDGFRA expression were associated with high tumour grade, high proliferation index and poor patient outcome. By fluorescence in situ hybridisation, no KIT amplification was found in carcinomas with high KIT expression, but two cases showed a relative gain of chromosome 4. In conclusion, no mutations of KIT or PDGFRA were found, but a subset of serous ovarian carcinoma showed overexpression of the proteins, which was associated with aggressive tumour characteristics.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian carcinoma

et al. 2004

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“…Platelet-derived growth factor and PDGFR have also been identified in metastatic ovarian carcinoma, with overexpression of PDGFR associated with poor prognosis (Dabrow et al, 1998). Pre-clinical studies in ovarian cancer xenograft models have shown increased efficacy for the combination of VEGFR and PDGFR tyrosine kinase inhibitors associated with decreased vessel coverage by pericytes supporting PDGF signalling as an antiangiogenic therapeutic target .…”

Section: Targeting Angiogenesis Through Alternative Pathwaysmentioning

confidence: 99%

Antiangiogenic drugs in ovarian cancer

2008

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“…PDGF receptors have been shown to be present in the theca and stroma compartments of porcine ovaries (Taylor 2000). PDGF has been demonstrated to affect the proliferation or function of both theca cells (Duleba et al 1999, Shores & Hunter 2000, Taylor 2000 and granulosa cells (Hammond et al 1985, Anderson & Lee 1993, Lafrance et al 1993, as well as ovarian surface epithelium (Dabrow et al 1998). No studies have been reported that examine any effect PDGF may have on the early stages of follicle development.…”

Section: Introductionmentioning

confidence: 99%

Platelet-derived growth factor modulates the primordial to primary follicle transition

Nilsson¹,

Detzel²,

Skinner³

2006

Reproduction

106

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Primordial follicles steadily leave the arrested pool and undergo a primordial to primary follicle transition during the female reproductive lifespan. When the available pool of primordial follicles is depleted reproduction ceases and humans enter menopause. The present study was designed to investigate the actions of several growth factors previously identified as candidate regulatory factors for the primordial to primary follicle transition with a microarray analysis. Ovaries from 4-day-old rats were placed into culture and treated for 2 weeks with platelet-derived growth factor (PDGF), anti-PDGF neutralizing antibody, vascular endothelial growth factor (VEGF), neuregulin (NRG), or kit ligand (KITL) as a positive control. PDGF-treatment resulted in a significant decrease in the percentage of primordial follicles and a concomitant increase in the percentage of developing primary follicles compared to controls. In contrast, ovaries treated with an anti-PDGF neutralizing antibody had a significant increase in the percentage of primordial follicles demonstrating an inhibition of endogenous follicle development. Ovaries incubated in the presence of VEGF or NRG had no change in follicle development. Observations indicate that PDGF, but not VEGF or NRG, promotes the primordial to primary follicle transition. Immunohistochemical localization indicated that the PDGF protein was present in the oocytes of both primordial and developing follicles. PDGF-treatment of cultured ovaries resulted in an increase in KITL mRNA expression. KITL has been previously shown to promote the primordial to primary follicle transition. KITLtreatment of ovaries had no effect on expression of Pdgf or any PDGF homologs or receptors. Therefore, PDGF appears to be produced by the oocyte and acts as one of several extracellular signaling factors that regulate the primordial to primary follicle transition. These observations provide insight into the cell-cell interactions involved in the regulation of primordial follicle development and can be used in the future development of therapies for some forms of infertility.

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The Effects of Platelet-Derived Growth Factor and Receptor on Normal and Neoplastic Human Ovarian Surface Epithelium

Cited by 90 publications

References 9 publications

Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian carcinoma

Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian carcinoma

Antiangiogenic drugs in ovarian cancer

Platelet-derived growth factor modulates the primordial to primary follicle transition

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