Reduction in tumour cell invasion by pigment epithelium-derived factor is mediated by membrane type-1 matrix metalloproteinase downregulation.
Prostate cancer and breast cancer are major killers among males and females respectively. In this study, pigment epithelium-derived factor (PEDF) was examined for its effect on commonly used human prostate cancer and human breast cancer cell lines. PEDF increased adhesion of cells to collagen-I, with decreased expression of phosphorylated focal adhesion kinase (p-Fak) consistent between the two cell types. Invasion of both tumour cell types through collagen-I was also reduced by PEDF, with decreased expression of membrane type-1 matrix metalloproteinase (MT1-MMP). These results were confirmed with specific antibodies to MT-MMP1. This study provides some vital clues as to which molecular players are perturbed by PEDF treatment of human prostate and breast cancer cells, raising hope that PEDF can in future be trialled against these major cancers in attempts to procure safer yet effective therapies for cancer.
School of Biomedical and Health Sciences, Victoria University, St Albans, Australia.
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D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects; D005136:Eye Proteins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D015843:Serpins / Q000494:pharmacology*; D000099174:Pigment Epithelium-Derived Factor
D024042:Collagen Type I; D005136:Eye Proteins; D053511:Matrix Metalloproteinase 14; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor