Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: Correlations with tumor invasion and metastasis

Shin Ichi Kurahara, Masanori Shinohara, Tetsuro Ikebe, Seiji Nakamura, Mahiro Beppu, Akimitsu Hiraki, Hiroshi Takeuchi, Kanemitsu Shirasuna

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

Background. Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential. Materials and Methods. This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined. Results. First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases. Conclusion. These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.

Original languageEnglish
Pages (from-to)627-638
Number of pages12
JournalHead and Neck
Volume21
Issue number7
DOIs
Publication statusPublished - Oct 11 1999

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Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases
Mouth
Squamous Cell Carcinoma
Neoplasm Metastasis
Extracellular Matrix
Neoplasms
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Staining and Labeling
Matrix Metalloproteinase 14
Tissue Inhibitor of Metalloproteinases
Lymph Nodes

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology

Cite this

Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity : Correlations with tumor invasion and metastasis. / Kurahara, Shin Ichi; Shinohara, Masanori; Ikebe, Tetsuro; Nakamura, Seiji; Beppu, Mahiro; Hiraki, Akimitsu; Takeuchi, Hiroshi; Shirasuna, Kanemitsu.

In: Head and Neck, Vol. 21, No. 7, 11.10.1999, p. 627-638.

Research output: Contribution to journalArticle

Kurahara, Shin Ichi ; Shinohara, Masanori ; Ikebe, Tetsuro ; Nakamura, Seiji ; Beppu, Mahiro ; Hiraki, Akimitsu ; Takeuchi, Hiroshi ; Shirasuna, Kanemitsu. / Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity : Correlations with tumor invasion and metastasis. In: Head and Neck. 1999 ; Vol. 21, No. 7. pp. 627-638.
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abstract = "Background. Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential. Materials and Methods. This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined. Results. First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases. Conclusion. These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.",
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T1 - Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity

T2 - Correlations with tumor invasion and metastasis

AU - Kurahara, Shin Ichi

AU - Shinohara, Masanori

AU - Ikebe, Tetsuro

AU - Nakamura, Seiji

AU - Beppu, Mahiro

AU - Hiraki, Akimitsu

AU - Takeuchi, Hiroshi

AU - Shirasuna, Kanemitsu

PY - 1999/10/11

Y1 - 1999/10/11

N2 - Background. Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential. Materials and Methods. This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined. Results. First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases. Conclusion. These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.

AB - Background. Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential. Materials and Methods. This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined. Results. First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases. Conclusion. These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.

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