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Chen, Jinfeng; Ye, Lin; Zhang, Lijian; Jiang, Wen Guo (2009)
Publisher: Spandidos Publications
Languages: English
Types: Article
Subjects: RC0254
Pigment epithelium-derived factor (PEDF) is an endogenous protein factor that has been shown to act as anti-angiognesis 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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    • 1. Tombran-Tink J and Johnson LV: Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30: 1700-1707, 1989.
    • 2. Tombran-Tink J, Chader GG and Johnson LV: PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res 53: 411-414, 1991.
    • 3. Steele FR, Chader GG, Johnson LV and Tombran-Tink J: Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci USA 90: 1526-1530, 1993.
    • 4. Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W and Bouck NP: Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285: 245-248, 1999.
    • 5. Duh EJ, Yang HS, Suzuma I, Miyagi M, Youngman E, Mori K, Katai M, Yan L, Suzuma K, West K, Davarya S, Tong P, Gehlbach P, Pearlman J, Crabb JW, Aiello LP, Campochiaro PA and Zack DJ: Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Invest Ophthalmol Vis Sci 43: 821-829, 2002.
    • 6. Aparicio S, Sawant S, Lara N, Barnstable CJ and Tombran-Tink J: Expression of angiogenesis factors in human umbilical vein endothelial cells and their regulation by PEDF. Biochem Biophys Res Commun 326: 387-394, 2005.
    • 7. Yamagishi S, Nakamura K, Matsui T, Inagaki Y, Takenaka K, Jinnouchi Y, Yoshida Y, Matsuura T, Narama I, Motomiya Y, Takeuchi M, Inoue H, Yoshimura A, Bucala R and Imaizumi T: Pigment epithelium-derived factor inhibits advanced glycation end product-induced retinal vascular hyperpermeability by blocking reactive oxygen species-mediated vascular endothelial growth factor expression. J Biol Chem 281: 20213-20220, 2006.
    • 8. Tong JP and Yao YF: Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions. Clin Biochem 39: 267-276, 2006.
    • 9. Yamagishi S, Nakamura K, Takenaka K, Matsui T, Jinnouchi Y and Imaizumi T: Pigment epithelium-derived factor (PEDF) promotes growth of pericytes through autocrine production of platelet-derived growth factor-B. Microvasc Res 69: 128-1234, 2005.
    • 10. Yabe T, Kanemitsu K, Sanagi T, Schwartz JP and Yamada H: Pigment epithelium-derived factor induces pro-survival genes through cyclic AMP-responsive element binding protein and nuclear factor kappa B activation in rat cultured cerebellar granule cells: Implication for its neuroprotective effect. Neuroscience 133: 691-700, 2005.
    • 11. Yabe T, Sanagi T, Schwartz JP and Yamada H: Pigment epithelium-derived factor induces pro-inflammatory genes in neonatal astrocytes through activation of NF-kappa B and CREB. Glia 50: 223-234, 2005.
    • 12. Uehara H, Miyamoto M, Kato K, Ebihara Y, Kaneko H, Hashimoto H, Murakami Y, Hase R, Takahashi R, Mega S, Shichinohe T, Kawarada Y, Itoh T, Okushiba S, Kondo S and Katoh H: Expression of pigment epithelium-derived factor decreases liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res 64: 3533-3537, 2004.
    • 13. Abramson LP, Browne M, Stellmach V, Doll J, Cornwell M, Reynolds M, Arensman RM and Crawford SE: Pigment epithelium-derived factor targets endothelial and epithelial cells in Wilms' tumour. J Pediatr Surg 41: 1351-1356, 2006.
    • 14. Zhang L, Chen J, Ke Y, Mansel RE and Jiang WG: Expression of pigment epithelial derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome. Int J Mol Med 17: 937-944, 2006.
    • 15. Guan M, Pang CP, Yam HF, Cheung KF, Liu WW and Lu Y: Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor. Cancer Gene Ther 11: 325-332, 2004.
    • 16. Hase R, Miyamoto M, Uehara H, Kadoya M, Ebihara Y, Murakami Y, Takahashi R, Mega S, Li L, Shichinohe T, Kawarada Y and Kondo S: Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice. Clin Cancer Res 11: 8737-8344, 2005.
    • 17. Streck CJ, Zhang Y, Zhou J, Ng C, Nathwani AC and Davidoff AM: Adeno-associated virus vector-mediated delivery of pigment epithelium-derived factor restricts neuroblastoma angiogenesis and growth. J Pediatr Surg 40: 236-243, 2005.
    • 18. Cheung LW, Au SC, Cheung AN, Ngan HY, Tombran-Tink J, Auersperg N and Wong AS: Pigment epithelium-derived factor is estrogen sensitive and inhibits the growth of human ovarian cancer and ovarian surface epithelial cells. Endocrinology 147: 4179-4191, 2006.
    • 19. Ek ET, Dass CR, Contreras KG and Choong PF: Inhibition of orthotopic osteosarcoma growth and metastasis by multitargeted antitumour activities of pigment epithelium-derived factor. Clin Exp Metastasis 24: 93-106, 2007.
    • 20. Guan M, Jiang H, Xu C, Xu R, Chen Z and Lu Y: Adenovirusmediated PEDF expression inhibits prostate cancer cell growth and results in augmented expression of PAI-2. Cancer Biol Ther 6: 419-425, 2007.
    • 21. Zhang L, Chen J, Ke Y, Mansel RE and Jiang WG: Downregulation of PEDF expression by ribozyme transgene in endothelial and lung cancer cells and its impact on angiogenesis in vitro. Oncol Rep 14: 1615-1619, 2005.
    • 22. Sobin LH and Fleming ID: TNM Classification of Malignant Tumours, fifth edition. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80: 1803-1804, 1997.
    • 23. Jiang WG, Davies G, Martin TA, Parr C, Watkins G, Mason MD, Mokbel K and Mansel RE: Targeting matrilysin and its impact on tumour growth in vivo: the potential implications in breast cancer therapy. Clin Cancer Res 11: 6012-6019, 2005.
    • 24. Jiang WG, Hiscox S, Hallett MB, Horrobin DF, Mansel RE and Puntis MC: Regulation of the expression of E-cadherin on human cancer cells by gamma-linolenic acid (GLA). Cancer Res 55: 5043-5048, 1995.
    • 25. Rosen EM, Meromsky L, Setter E, Vinter DW and Goldberg ID: Smooth muscle-derived factor stimulates mobility of human tumour cells. Invasion Metastasis 10: 49-64, 1990.
    • 26. Jiang WG, Sampson J, Martin TA, Lee-Jones L, Watkins G, Douglas-Jones A, Mokbel K and Mansel RE: Tuberin and hamartin are aberrantly expressed and linked to clinical outcome in human breast cancer: the role of promoter methylation of TSC genes. Eur J Cancer 41: 1628-1636, 2005.
    • 27. Abe R, Shimizu T, Yamagishi S, Shibaki A, Amano S, Inagaki Y, Watanabe H, Sugawara H, Nakamura H, Takeuchi M, Imaizumi T and Shimizu H: Overexpression of pigment epithelium derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. Am J Pathol 164: 1225-1232, 2004.
    • 28. Guan M, Yam HF, Su B, Chan KP, Pang CP, Liu WW, Zhang WZ and Lu Y: Loss of pigment epithelium derived factor expression in glioma progression. J Clin Pathol 56: 277-282, 2003.
    • 29. Cai J, Parr C, Watkins G, Jiang WG and Boulton M: Decreased pigment epithelium-derived factor expression in human breast cancer progression. Clin Cancer Res 12: 3510-3517, 2006.
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