PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells

Carcinogenesis. 2004 Sep;25(9):1587-92. doi: 10.1093/carcin/bgh171. Epub 2004 Apr 29.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Division
  • Cell Movement*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Invasiveness*
  • Progranulins
  • Tamoxifen / pharmacology
  • Tumor Cells, Cultured
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Anticarcinogenic Agents
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Vascular Endothelial Growth Factor A
  • Tamoxifen
  • Matrix Metalloproteinase 9