The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance.
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.
Chen
Jinfeng
J
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100036, P.R. China.
Ye
Lin
L
Zhang
Lijian
L
Jiang
Wen G
WG
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000818:Animals; D016466:CHO Cells; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D015843:Serpins; D025521:Tumor Suppressor Proteins; D000099174:Pigment Epithelium-Derived Factor