Carcinogenesis Advance Access originally published online on April 29, 2004
Carcinogenesis 2004 25(9):1587-1592; doi:10.1093/carcin/bgh171
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Carcinogenesis vol.25 no.9 © Oxford University Press 2004; all rights reserved.
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PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells
1 A&G Pharmaceutical Inc., Columbia, Maryland, 2 Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland and 3 Program in Oncology, Greenebaum Cancer Center of the University of Maryland, Baltimore, Maryland, USA
4 To whom correspondence should be addressed Email: gserrero{at}agrx.net
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.
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