Tumor Cell Invasion Inhibited by TIMP-2

Albini, Adriana; Melchiori, A; Santi, Leonardo; Liotta, Lance A.; Brown, Peter de Nully; Stetler-Stevenson, William G.

doi:10.1093/jnci/83.11.775

Cited by 291 publications

(127 citation statements)

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“…1). Similar anti-invasive properties have previously been reported with other hydroxamic acid based MMPIs [35][36][37] and TIMPs [38][39][40], as well as with anti-gelatinases anti-bodies [39,41]. Because a reduced invasiveness could result from a cytotoxic effect of the inhibitor, cellular viability and metabolism were measured by the WST-1 assay after 48 h of treatment.…”

Section: Anti-invasive Activity Of Gi129471 On Ht1080 Cellssupporting

confidence: 62%

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Maquoi

Munaut

Colige

et al. 2002

Experimental Cell Research

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Enhanced expression and activation of matrix met-alloproteinase-2 (MMP-2) and MMP-9 have been associated with tumor progression, invasion, and metastasis. The use of synthetic MMP inhibitors to block the proteolytic activity of these enzymes recently emerged as a potential therapeutic tool to treat cancer. In this study, we report that GI129471, a synthetic broad-spectrum MMP inhibitor, efficiently reduced the in vitro invasiveness of HT1080 cells through type IV collagen, a major component of basement membranes. This reduced invasion was paralleled by a complete inhibition of pro-MMP-2 activation; however, GI129471 strongly increased the amount of secreted pro-MMP-9, which could be subsequently activated through a plasminogen-dependent mechanism. Quantitative RT-PCR and northern blot analysis revealed that GI129471 specifically increased the MMP-9 mRNA steady-state level. Moreover, transient transfection of HT1080 cells with β-galactosidase reporter vectors containing different lengths of the 5'-flanking region of the MMP-9 gene revealed an upregulation of the transcriptional activity of the corresponding promoter. Well-known modulators of MMP-9 expression such as 11-1β and TNF-α were not involved in this upregulation. These findings emphasize the complexity of the regulation of MMP expression and the requirement for a detailed characterization of the potential adverse side effects associated with the use of broad-Spectrum MMPIs.

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Section: Anti-invasive Activity Of Gi129471 On Ht1080 Cellssupporting

confidence: 62%

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Maquoi

Munaut

Colige

et al. 2002

Experimental Cell Research

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“…20 It was long been believed that TIMPs suppressed tumor invasion by inhibiting MMPs in experimental and clinical studies. Recombinant TIMP-2 inhibited the invasion of HT-1080 fibrosarcoma cells in vitro 21 ; and increased TIMPs expression has been correlated with decreased tumor growth, invasiveness, and metastasis in tumor cell lines of the stomach, 22 pancreas, 23 and lung. 24 However, the current study demonstrated that TIMP-2 immunoreactivity was correlated positively with the degree of malignant behavior in thymomas, contrary to previous evidence.…”

Section: Discussionmentioning

confidence: 96%

Characteristics of primary care physicians and their practices associated with mammography rates for older women

Harrison

Janz

Wolfe

et al. 2003

Cancer

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BACKGROUND Mammography screening rates are below national recommendations for older women. Understanding the relation between the characteristics of primary care physicians (PCPs) and mammography rates for older women can help to target screening improvement efforts. METHODS Subjects were 2527 PCPs practicing in Michigan between 1997 and 1998. A cross‐sectional design used Medicare data to identify women age 68 years or older in 1998 whom PCPs treated in 1997–1998 and to determine whether these women had a mammogram between 1996 and1998. Eligible women were Medicare beneficiaries age 65 years or older by 1996, residing in Michigan from 1996 to 1998, without specified comorbidities likely to affect decisions regarding mammography. Correlations and multiple regressions examined the relation between this score and characteristics of both PCPs and their practice populations of older women. RESULTS Mammography rates across physicians' practices ranged from 3–100% (mean = 59%, standard deviation = 17%). Five predictors accounted for 55% of the variance in mammography rates across practices. Higher mammography rates were found to be independently related to physicians who have: a lower mean age for female Medicare patients, a higher mean number of physicians billing for patients' care, a lower mean number of inpatient admissions, obstetrics/gynecology practices, and a higher mean education level in patient's zip code (beta weights ≥ 0.25, P < 0.0001). CONCLUSIONS PCPs vary substantially with regard to mammography rates for older women. Mammography rates vary more with the population of patients in physicians' practices than with commonly measured personal characteristics of physicians. Mammography rates should be adjusted for patient population to target individual PCPs with low mammography rates for interventions. Cancer 2003. © 2003 American Cancer Society.

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“…The levels of MMP-2 and MMP-9 in high-grade or invasive bladder cancers were found to be significantly higher than those in low-grade and non-invasive bladder cancers, indicating that MMP-2 and MMP-9 may play a role in the invasion and metastasis of bladder cancer (Davies et al, 1993). TIMPs are known for their anti-neoplastic activity (Albini et al, 1991;Montgomery et al, 1994). The transfection of sense TIMP-I complementary DNA into metastatic cells decreased their invasive, tumorigenic and metastatic capacities (DeClerck et al, 1992;Khokha et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the imbalance of these enzymes and inhibitors is most likely an important factor in urothelial cancer invasion and metastasis, and, thereby, recurrence. There have been several studies on the inhibition of tumour invasion and metastasis by TIMP-1 (Schultz et al, 1988;Alvarez et al, 1990) and TIMP-2 (Albini et al, 1991;DeClerck et al, 1991). Koop et al (1994) found that the decreased metastatic ability of TIMP-overexpressing B 16F10 melanoma cells was due to the effects of TIMP on tumour growth after tumour cell extravasation in the metastatic target organ.…”

Section: Discussionmentioning

confidence: 99%

Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer

Gohji

Fujimoto²,

Ohkawa³

et al. 1998

Br J Cancer

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Summary Serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were evaluated as prognostic indicators of the recurrence of urothelial cancer. Sera were obtained from 127 healthy control subjects and 97 urothelial cancer patients who underwent complete resection and were measured for MMP-2 and TIMP-2 using a one-step enzyme immunoassay. The relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of urothelial cancer was examined. The mean serum MMP-2/TIMP-2 ratio in the 31 advanced urothelial cancer patients with recurrence was significantly higher than that in the 22 patients without recurrence (P = 0.0029) and in the 44 superficial bladder cancer patients (P < 0.0001). The 1-and 3-year disease-free survival rates in the patients with high MMP-2/TIMP-2 ratios (50% and 12%) were significantly poorer than those of the patients with normal ratios (82% and 56%) (P=0.0152). Univariate and multivariate analyses of recurrence demonstrated that the serum MMP-2/TIMP-2 ratio is a significant independent indicator of advanced urothelial cancer. Our results indicate that an imbalance between the serum levels of MMP-2 and TIMP-2 could be a new predictor of recurrence in advanced urothelial cancer patients.Keywords: serum; matrix metalloproteinase-2; tissue inhibitor of metalloproteinases-2; urothelial cancer; recurrence Matrix metalloproteinases (MMPs) has been shown to play a role in the degradation of the vascular basement membrane, whose major component is type IV collagen Nakajima et al, 1991). Matrix metalloproteinase-2 (MMP-2, gelatinase A, a 72-kDa type IV collagenase) is produced by both malignant cells and stromal cells such as fibroblasts, macrophages and vascular endothelial cells (Nakajima et al, 1991). Many investigators have demonstrated that human and rodent metastatic malignant cells produce larger amounts of MMP-2 than do non-metastatic cells, both in vitro and in vivo (Liotta et al, 1980;. Tissue inhibitor of metalloproteinases-2 (TIMP-2), an unglycosylated protein of 21-kDa molecular weight, strongly inhibits the biological activity of MMP-2, and was shown to strongly inhibit cancer invasion, metastasis, growth and angiogenesis in some rodent and human tumours (Stetler-Stevenson et al, 1989;DeClerck et al, 1992). Therefore, it is likely that an imbalance in the MMP-2 and TIMP-2 ratio plays an important role in cancer invasion, metastasis and angiogenesis DeClerck et al, 1994). Some investigators have revealed a relationship between the recurrence and the expression of MMP-2 and TIMP-2 in bladder cancer tissues (Davies et al, 1993;Grignon et al, 1996). However, there are no previous reports concerning the relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of human urothelial cancer. In this study, the serum levels of MMP-2 and TIMP-2 were determined in human urothelial cancer patients, and the relationship between the serum MMP-2/TIMP-2 ratio and invasion and metastasis in urothelial cancer was examined. We discuss the diagno...

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Tumor Cell Invasion Inhibited by TIMP-2

Cited by 291 publications

References 0 publications

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Characteristics of primary care physicians and their practices associated with mammography rates for older women

Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer

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