Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma

Koshiba, Takatomo; Hosotani, Ryo; Wada, Michihiko; Miyamoto, Yoshiharu; Fujimoto, Koji; Lee, Jeon-Uk; Doi, Ryuichiro; Arii, Shigeki; Imamura, Masayuki

doi:10.1002/(sici)1097-0142(19980215)82:4<642::aid-cncr5>3.0.co;2-n

Cited by 142 publications

(79 citation statements)

References 20 publications

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“…Similarly, expression of activated MMP-2 is related to regional lymph node and distal metastasis as well as to postresection recurrence of the same tumour. 56 Concomitant overexpression of MMP-2 and MMP-7 is associated with recurrence in hepatocellular cancer, 57 and elevated MMP-9 expression in tumor cells is related to recurrence in superficial carcinoma of the urinary bladder. 58 The expression of certain MMPs in primary tumour can predict the risk of metastasis.…”

Section: Mmps As Predictors Of Recurrence or Metastasis Riskmentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

582

484

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Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer.

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Section: Mmps As Predictors Of Recurrence or Metastasis Riskmentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

582

484

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“…Thus, the net MMP activity is the result of the balance between activated enzyme levels and TIMP levels. The overproduction and unrestrained activity of MMPs have been linked to malignant conversion of tumor cells (Bernhard et al, 1994;Koshiba et al, 1998;Sehgal et al, 1998;Coussens et al, 1999;Sternlicht et al, 1999;Coussens et al, 2000). Decreased production of TIMP could also result in greater e ective enzyme activity and invasive potential (Denhardt et al, 1992;Khokha et al, 1989).…”

Section: Old Paradigm: Inhibition Of Tumorigenesis and Tumor Metastasmentioning

confidence: 99%

Complex roles of tissue inhibitors of metalloproteinases in cancer

2002

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Matrix metalloproteinases (MMPs) is tightly associated with extracellular matrix (ECM) turnover, which plays a very active role in tumor invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMPs) plays a critical role in the homeostasis of ECM by regulating the activity of MMPs. TIMPs are well-known for their ability to inhibit MMP activity thereby inhibiting tumor growth and metastasis. However, many evidences suggest that TIMPs are multifunctional proteins, which regulate cell proliferation, apoptosis, proMMP-2 activation, and angiogenesis. These e ects may be through MMPdependent or MMP-independent pathways. Recent data indicate that TIMPs have many paradoxical roles in tumorigenesis. In particular, both inhibitory e ect and stimulatory e ect on tumorigenesis have been demonstrated in many animal models in which TIMPs were overexpressed in cancer cells or in mice. Elevated TIMP levels are reported in association with cancer progression and identi®ed as poor prognostic indicators in several human tumor types. Herein, we review the complex roles of TIMPs in cancer growth and metastasis.

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“…Previous studies have shown that active MMP-2 is expressed in a variety of tumour types, including gastric carcinoma [5,6], colorectal carcinoma [6], pancreatic carcinoma [7], breast cancer [8] and bladder cancer [9]. In urothelial cancer, tumour cell in®ltration into muscle layers, surrounding tissue or vessels is associated with local recurrence, metastasis and a poor outcome [10].…”

Section: Introductionmentioning

confidence: 99%

The role of the activated form of matrix metalloproteinase‐2 in urothelial cancer

et al. 2000

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Objective To investigate the expression of matrix metalloproteinase-2 (MMP-2, reportedly associated with cancer cell invasion and metastasis in many human cancers) in urothelial tumours and thus de®ne its role in this disease. Materials and methods The expression of both the activated form of MMP-2 and total MMP-2 (activated + latent form) was measured using gelatine zymography in tissue obtained surgically from 61 patients with urothelial cancer. The correlation between the level of the activated form of MMP-2 and clinical and histological variables was assessed. Results The expression of activated and total MMP-2 were signi®cantly higher in invasive tumour tissue and both levels were correlated with histological grade. In particular, the level of activated MMP-2 was more closely correlated than that of total MMP-2 in invasive tumour tissue. Moreover, high levels of activated MMP-2 were strongly associated with shorter disease-speci®c survival (P=0.0016). Conclusion These ®ndings suggest that activated MMP-2 plays a signi®cant role in invasion of urothelial cancer and that the level of activated MMP-2 expression is a useful prognostic indicator.

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Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma

Abstract: The results of the current study indicate that MMP-2 activation plays a significant role in tumor invasion and metastasis in pancreatic carcinoma.

Cited by 142 publications

References 20 publications

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Complex roles of tissue inhibitors of metalloproteinases in cancer

The role of the activated form of matrix metalloproteinase‐2 in urothelial cancer

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