Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells

Kei Matsuda, Haruhisa Maruyama, Fang Guo, Jörg Kleeff, Jun Itakura, Yoshiro Matsumoto, Arthur D. Lander, Murray Korc

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

Glypicans are a family of glycosylphosphatidylinositol-anchored cell surface heparan sulfate proteoglycans implicated in the control of cellular growth and differentiation. Here we show that glypican-1 is strongly expressed in human breast cancers, whereas expression of glypican-1 is low in normal breast tissues. In contrast, the expression of glypican-3 and -4 is only slightly increased in breast cancers by comparison with normal breast tissues, and glypican-2 and -5 are below the level of detection by Northern blotting in both normal and cancer samples. Treatment of MDA-MB-231 and MDA-MB-468 breast cancer cells with phosphoinositide-specific phospholipase-C abrogated the mitogenic response to two heparin-binding growth factors, heparin-binding epidermal growth factor-like growth factor and fibroblast growth factor 2. Stable transfection of these cells with a glypican-1 antisense construct markedly decreased glypican-1 protein levels and the mitogenic response to the same heparin-binding growth factors, as well as that to heregulin α, heregulin β, and hepatocyte growth factor. Syndecan-1 was also expressed at high levels in both breast cancer tissues and breast cancer cells when compared with normal breast tissues. There was a good correlation between glypican-1 and syndecan-1 expression in the tumors. However, clones expressing the glypican-1 antisense construct did not exhibit decreased syndecan-1 levels, indicating that loss of responsiveness to heparin-binding growth factors in these clones was not due to altered syndecan-1 expression. Furthermore, 8 of 10 tumors with stage 2 or 3 disease exhibited high levels of glypican-1 by Northern blot analysis. In contrast, low levels of glypican-1 mRNA were evident in 1 of 10 tumors with stage 2 or 3 disease and in 9 of 10 tumors with stage 1 disease. Taken together, these data suggest that glypican-1 may play a pivotal role in the ability of breast cancer cells to exhibit a mitogenic response to multiple heparin-binding growth factors and may contribute to disease progression in this malignancy.

Original languageEnglish (US)
Pages (from-to)5562-5569
Number of pages8
JournalCancer Research
Volume61
Issue number14
StatePublished - Jul 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Matsuda, K., Maruyama, H., Guo, F., Kleeff, J., Itakura, J., Matsumoto, Y., Lander, A. D., & Korc, M. (2001). Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Research, 61(14), 5562-5569.