Pigment Epithelium-Derived Factor Is Estrogen Sensitive and Inhibits the Growth of Human Ovarian Cancer and Ovarian Surface Epithelial Cells

Cheung, Lydia W.T.; Au, Simon C.L.; Cheung, Annie Nga‐Yin; Ngan, Hextan Y.S.; Tombran-Tink, Joyce; Auersperg, Nelly; Wong, Alice S.T.

doi:10.1210/en.2006-0168

Cited by 84 publications

(67 citation statements)

References 37 publications

(32 reference statements)

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“…17 To date, a few studies have tested the therapeutic potential of PEDF against a number of tumor models, both in vitro and in vivo, and have demonstrated inhibition of growth and the suppression of metastasis in cancers, such as pancreatic carcinoma, 18 prostate carcinoma, 19 melanoma, 20 neuroblastoma 21 and ovarian cancer. 22 In these studies, however, all have used models that have developed following ectopic implantation of cancer cell lines. Hence, no paper has reported the role and antitumor effect of PEDF in an orthotopic model of cancer (i.e., a tumor grown within its organ of origin).…”

Section: Introductionmentioning

confidence: 99%

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Dass

Contreras

et al. 2007

Cancer Gene Ther

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Despite significant improvements, the current management of primary osteosarcoma is still limited by the development of metastatic disease, which occurs in approximately 30% of patients despite aggressive multiagent chemotherapy and tumor-ablative surgery. Therefore, there is a need for the development of novel agents to improve the outcome of these patients. Pigment epithelium-derived factor (PEDF) has been shown to be one of the most potent inhibitors of angiogenesis, and more recently has demonstrated a functional role in tumor growth, invasion and metastasis. In this study we report, for the first time, the multitargeted role of PEDF in the inhibition of growth, angiogenesis and metastasis of two orthotopic models of osteosarcoma (rat UMR 106-01 and human SaOS-2). Through stable plasmid-mediated gene transfer of full-length human PEDF, we show that PEDF overexpression significantly reduced tumor cell proliferation (Po0.05) and Matrigel invasion (UMR PEDF , Po0.001; SaOS PEDF , Po0.05) and increased adhesion to collagen type-1 (Po0.01), in vitro. In vivo, PEDF overexpression dramatically suppressed orthotopic osteosarcoma growth (Po0.05) and the development of spontaneous pulmonary metastases (UMR PEDF , Po0.05; SaOS PEDF , Po0.001). Furthermore, PEDF-overexpressing tumors exhibited reduced intratumoral angiogenesis, evidenced by a significant decrease in microvessel density (Po0.05). Therefore, together these results suggest that PEDF may be a new and promising approach for the treatment of osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Dass

Contreras

et al. 2007

Cancer Gene Ther

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“…33 Cheung and colleagues in 2006 found that ER is an important upstream regulator of PEDF in human ovarian cancer and ovarian surface epithelial cells. 34 They found that E2 reduced PEDF levels, and that this process could be prevented by the total ER antagonist, ICI 182,780.…”

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confidence: 99%

Effects of Tamoxifen Versus Raloxifene on Retinal Capillary Endothelial Cell Proliferation

Grigsby

Parvathaneni

Almanza

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Endothelial cell proliferation in angiogenesis is active in conditions such as cancers and diabetic retinopathy. Tamoxifen (T) and raloxifene (R) have been compared in numerous studies as a prophylaxis for breast cancer, and T is used to treat breast cancer. T, unlike R, has been linked to an increase in uterine cancers, thrombo-embolic events, and cataract. The purpose of our study was to evaluate the efficacies of T and R in reducing estrogen-induced retinal capillary endothelial cell proliferation. Methods: Rhesus monkey retinal capillary endothelial cells (ATCC RF/6A) were used to assay cell proliferation when treated with 0.0, 0.1, 1.0, and 10.0 nM 17 b estradiol (E2) for 24 and 48 h. Viable cells were counted using a Neubauer hemocytometer with a trypan blue exclusion method to determine the number of viable cells. Cell counts were also performed using 1.0 nM E2 with 0.01, 0.1, 1.0, and 10.0 nM concentrations of either T or R. Cell medium, collected at 24 h, was evaluated for vascular endothelial growth factor and pigment epithelium-derived factor. Results: Viable cells were significantly greater in cultures treated with 1.0 or 10.0 nM E2, compared to cells treated with 0.0 or 0.1 nM E2 both at 24 and 48 h. Viable cell counts were reduced significantly in cultures treated with 0.1, 1.0, or 10.0 nM T or R in addition to the 1.0 nM E2. Cell counts were not significantly different when comparing equal concentrations of T and R, that is, 1.0 nM E2 + 1 nM T or R. Vascular endothelial growth factor and pigment epithelium-derived factor protein/10,000 cells was reduced by 1.0 nM E2, but returned to higher levels with the introduction of T and R to growth media. Conclusions: T and R showed similar potency in inhibiting estrogen-induced retinal capillary endothelial cell proliferation. Considering drug safety profiles, our results, when extended to animals and humans, suggest that R is preferable to T in treating angiogenic retinal diseases. Further studies on the signaling mechanism of estrogen-induced endothelial cell proliferation may lead to new treatment strategies in the treatment of ocular angiogenic diseases.

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“…PEDF has been shown to have a potential function to inhibit cancer, including osteosarcoma, ovarian carcinoma and prostate cancer (18)(19)(20). Our previous study showed that high levels of PEDF expression in lung cancer tissue were correlated with patients prognosis and that PEDF was an important factor in lung cancer development (14).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that this link to prognosis is the result of increased angiogenesis in the tumour due to the loss of anti-angiogenic control by PEDF. However, it has been recently shown that when engineered to express PEDF, certain cancer cells, such as prostate cancer, osteosarcoma, ovarian cancer, pancreatic cancer, malignant glioma, neuroblastoma, have a reduced growth rate, thus arguing for a potential direct effect of PEDF on cancer cells (15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance

Chen

Ye²,

Zhang³

et al. 2009

Int J Oncol

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Abstract. Pigment epithelium-derived factor (PEDF) is an endogenous protein factor that has been shown to act as antiangiognesis factor. The present study aimed to determine the direct biological effects of PEDF on lung cancer cells and deduce a clinical relevance in patients with lung cancer, major cause of death worldwide in which the knowledge of PEDF remains poor. We constructed a mammalian expression system for human PEDF produced recombinant PEDF (rhPEDF) protein from 3T3 cells. The expression of PEDF was examined using SDS-PAGE and Western blot analysis. Using the rhPEDF protein, we investigated the biological function of PEDF in the lung cancer cells as well as endothelial cells. PEDF expression levels were assessed in a cohort of human lung cancer specimen (77 pairs of matched normal and tumour tissues), in association with patient clinical variables and survival, using quantitative analysis of PEDF. In vitro, we found that administration of rhPEDF on two lung cancer cell lines (A549 and SK-MES1) significantly reduced tumour cell growth (P<0.05) with no significant effect on the growth of vascular cell line (HECV). We also found that rhPEDF significantly decreased lung cancer motility and adhesion to extracellular matrix (Matrigel) when compared with the control cells (P<0.05). We showed that reduced PEDF levels in lung cancer tissues significantly correlated with lymph node metastasis and an overall poor prognosis in the lung cancer patients. PEDF suppresses the growth and motility of lung cancer cells and has a significant correlation with the clinical outcome of the patients. These results contribute to our understanding of the molecular mechanisms of PEDF and indicates a potential prognostic and therapeutic impact of PEDF in lung cancer.

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Pigment Epithelium-Derived Factor Is Estrogen Sensitive and Inhibits the Growth of Human Ovarian Cancer and Ovarian Surface Epithelial Cells

Cited by 84 publications

References 37 publications

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Effects of Tamoxifen Versus Raloxifene on Retinal Capillary Endothelial Cell Proliferation

The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance

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