Granulocyte-macrophage colony-stimulating factor upregulates matrix metalloproteinase-2 (MMP-2) and membrane type-1 MMP (MT1-MMP) in human head and neck cancer cells

Toshiki Tomita, Masato Fujii, Yutaka Tokumaru, Yorihisa Imanishi, Minoru Kanke, Taku Yamashita, Ryuichiro Ishiguro, Jin Kanzaki, Kaori Kameyama, Yoshihide Otani

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Matrix metalloproteinase-2 (MMP-2) and membrane type 1-MMP (MT1-MMP) play an important role in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC), but the mechanism of their regulation is not clearly understood. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be associated with cancer invasion and metastasis. We hypothesized that GM-CSF may upregulate MMP-2 and/or MT1-MMP expression in HNSCC cells, and may thereby influence their ability to invade and metastasize. We studied the effects of GM-CSF on the production of MMP-2 and MT1-MMP in HNSCC cell lines SAS and HSC-2. Gelatin zymography of conditioned media derived from HNSCC cells revealed a major band of 68 kDa, which was characterized as proMMP-2. GM-CSF stimulated the production of proMMP-2 in both cell lines in a dose-dependent manner. Treatment with 50 ng/ml GM-CSF for 24 h increased the proMMP-2 activity 3.4-fold in SAS cells and 2.3-fold in HSC-2 cells compared with untreated controls. Northern blot analyses demonstrated that GM-CSF led to elevated mRNA levels of MMP-2 and MT1-MMP in both cell lines. The results identify GM-CSF as a regulator of MMP-2 and MT1-MMP expression in certain types of HNSCC, and suggest that GM-CSF may contribute to the invasiveness of HNSCC through the regulation of MMP-2 and MT1-MMP expression. Copyright (C) 2000 Elsevier Science Ireland Ltd.

元の言語English
ページ(範囲)83-91
ページ数9
ジャーナルCancer Letters
156
発行部数1
DOI
出版物ステータスPublished - 2000 8 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tomita, T., Fujii, M., Tokumaru, Y., Imanishi, Y., Kanke, M., Yamashita, T., Ishiguro, R., Kanzaki, J., Kameyama, K., & Otani, Y. (2000). Granulocyte-macrophage colony-stimulating factor upregulates matrix metalloproteinase-2 (MMP-2) and membrane type-1 MMP (MT1-MMP) in human head and neck cancer cells. Cancer Letters, 156(1), 83-91. https://doi.org/10.1016/S0304-3835(00)00446-8