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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalCancer Letters
Volume156
Issue number1
DOIs
Publication statusPublished - 2000 Aug 1

Fingerprint

Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
Granulocyte-Macrophage Colony-Stimulating Factor
Head and Neck Neoplasms
Matrix Metalloproteinases
Up-Regulation
Membranes
Cell Line
Matrix Metalloproteinase 15
Neoplasm Metastasis
Gelatin
Conditioned Culture Medium
Northern Blotting
Carcinoma, squamous cell of head and neck
Messenger RNA

Keywords

  • Granulocyte-macrophage colony-stimulating factor
  • Head and neck squamous cell carcinoma
  • Matrix metalloproteinase-2
  • Membrane type 1 matrix metalloproteinase

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

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

In: Cancer Letters, Vol. 156, No. 1, 01.08.2000, p. 83-91.

Research output: Contribution to journalArticle

Tomita, Toshiki ; Fujii, Masato ; Tokumaru, Yutaka ; Imanishi, Yorihisa ; Kanke, Minoru ; Yamashita, Taku ; Ishiguro, Ryuichiro ; Kanzaki, Jin ; Kameyama, Kaori ; Otani, Yoshihide. / 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. In: Cancer Letters. 2000 ; Vol. 156, No. 1. pp. 83-91.
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abstract = "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.",
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AU - Tomita, Toshiki

AU - Fujii, Masato

AU - Tokumaru, Yutaka

AU - Imanishi, Yorihisa

AU - Kanke, Minoru

AU - Yamashita, Taku

AU - Ishiguro, Ryuichiro

AU - Kanzaki, Jin

AU - Kameyama, Kaori

AU - Otani, Yoshihide

PY - 2000/8/1

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N2 - 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.

AB - 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.

KW - Granulocyte-macrophage colony-stimulating factor

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