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

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Chen, Jinfeng ; Ye, Lin ; Zhang, Lijian ; Jiang, Wen Guo (2009)

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.
  • References (29)
    29 references, page 1 of 3

    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.

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