PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells.
Metastasis is a multi-step process involved in the progression of breast cancer to a disease with poor prognosis. Growth factor and/or growth factor receptor over- expression have been reported to play an important role in this process. The 88 kDa glycoprotein PC cell-derived growth factor (PCDGF/GP88), also known as progranulin, has been shown to play a major role in breast tumorigenesis by stimulating proliferation, mediating survival and conferring resistance to tamoxifen. In the present paper, the metastatic potential of PCDGF/GP88 was examined in breast cancer. Using MCF-7 cells, we showed that PCDGF/GP88 over-expression stimulated anchorage-independent cell growth and accelerated cell migration through matrigel. Similar results were obtained with MCF-7 cells treated exogenously with PCDGF/GP88. Furthermore, gelatin zymograph and immunoblot revealed that matrix metalloprotease-9 was up-regulated by PCDGF/GP88. PCDGF/GP88 stimulated VEGF expression in MCF-7 cells. These results suggest that PCDGF/GP88 could act to promote metastasis and angiogenesis in human breast cancer cells in addition to stimulating their proliferation and survival.
Tangkeangsirisin
Wisit
W
A and G Pharmaceutical Inc., Columbia, Maryland, USA.
Serrero
Ginette
G
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000077153:Progranulins; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; D020780:Matrix Metalloproteinase 9