Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma

Yorihisa Imanishi, Masato Fujii, Yutaka Tokumaru, Toshiki Tomita, Minoru Kanke, Jin Kanzaki, Kaori Kameyama, Yoshihide Otani, Hiroshi Sato

Research output: Contribution to journalArticle

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Abstract

Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P= .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC. Copyright (C) 2000 by W.B. Saunders Company.

Original languageEnglish
Pages (from-to)895-904
Number of pages10
JournalHuman Pathology
Volume31
Issue number8
DOIs
Publication statusPublished - 2000

Fingerprint

Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
Messenger RNA
Neoplasm Metastasis
human MMP2 protein
Carcinoma, squamous cell of head and neck
Matrix Metalloproteinase 15
Membrane-Associated Matrix Metalloproteinases
Lymph Nodes
Immunohistochemistry
Carcinoma
Cell Line
Stromal Cells
Matrix Metalloproteinases

Keywords

  • HNSCC
  • Lymph node metastasis
  • MMP-2
  • MT1-MMP
  • Multivariate logistic regression analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma. / Imanishi, Yorihisa; Fujii, Masato; Tokumaru, Yutaka; Tomita, Toshiki; Kanke, Minoru; Kanzaki, Jin; Kameyama, Kaori; Otani, Yoshihide; Sato, Hiroshi.

In: Human Pathology, Vol. 31, No. 8, 2000, p. 895-904.

Research output: Contribution to journalArticle

Imanishi, Yorihisa ; Fujii, Masato ; Tokumaru, Yutaka ; Tomita, Toshiki ; Kanke, Minoru ; Kanzaki, Jin ; Kameyama, Kaori ; Otani, Yoshihide ; Sato, Hiroshi. / Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma. In: Human Pathology. 2000 ; Vol. 31, No. 8. pp. 895-904.
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T1 - Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma

AU - Imanishi, Yorihisa

AU - Fujii, Masato

AU - Tokumaru, Yutaka

AU - Tomita, Toshiki

AU - Kanke, Minoru

AU - Kanzaki, Jin

AU - Kameyama, Kaori

AU - Otani, Yoshihide

AU - Sato, Hiroshi

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AB - Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P= .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC. Copyright (C) 2000 by W.B. Saunders Company.

KW - HNSCC

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KW - Multivariate logistic regression analysis

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