Enhanced expression of tissue inhibitor of metalloproteinase‐2 (TIMP‐2) in the stroma of breast carcinomas correlates with tumor recurrence

Visscher, Daniel W.; Höyhtyä, Matti; Ottosen, Susan; Liang, Chi-Ming; Sarkar, Fazlul H.; Crissman, John D.; Fridman, Rafael

doi:10.1002/ijc.2910590308

Cited by 154 publications

(100 citation statements)

References 13 publications

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“…Pro-MMP-2 in the ternary complex is activated by MT1-MMP that is free from TIMP-2. [25][26][27] Recently, some studies reported that TIMP-2 plays a positive role in invasion and metastasis in carcinoma of the breast, 28 lung, 29 colon, 30 and bladder. 31 The current study demonstrated that both MMP-2 and TIMP-2 were detected mostly on the tumor cell surface and cytoplasm of thymomas and that they stained more strongly in border areas between the tumor and the stroma, which was the invasive area, compared with the central area of the tumor.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Immunoreactivity was visualized by successive incubations with alkaline phosphatase-conjugated goat anti-mouse (or antirabbit for TIMP-1) IgG and color developing substrates. The preparation of mAb against human progelatinase A, progelatinase B and TIMP-2 were previously described [26,27]. The rabbit polyclonal antiserum against human TIMP-1 was kindly provided by Dr. Chua (Wayne State University).…”

Section: Immunoblot Analysismentioning

confidence: 99%

The extracellular matrix produced by bovine corneal endothelial cells contains progelatinase A

Ménashi¹,

Vlodavsky²,

Ishai-Michaeli³

et al. 1995

FEBS Letters

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Progelatinase A is a matrix metalloproteinase involved in the turnover of extracellular matrix (ECM). We report that the ECM produced by bovine corneal endothelial (BCE) cells contains progelatinase A free of tissue inhibitor of metalloproteinase (TIMP2). The matrix-bound progelatinase A can be activated by APMA to generate a 62 kDa and a 45 kDa species with enzymatic activity and is inhibited by TIMP2. The bound progelatinase can be released after treatment of the ECM with gelatinase B. These studies suggest that the ECM can function as a reservoir for progelatinase A which may be readily available for cells in processes such as metastasis, angiogenesis, inflammation and wound heating.

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“…The findings seem to be contradictory to the proposed role of TIMP-1 as a tumour metastasis suppressor: if TIMP-1 acts as a functional inhibitor of tumour invasion and metastasis, its expression should inversely correlate with the aggressiveness of thyroid tumours. Indeed, such an inverse association has been documented in several (Albini et al, 1991;DeClerck et al 1991DeClerck et al , 1992Ponto et al, 1991;Khoka et al, 1992Khoka et al, , 1994Montgomery et al, 1994) but not all (Kussakowska et al, 1991;Lu et al, 1991;Visscher et al, 1994aVisscher et al, , 1994bNakana et al, 1995;Zeng et al, 1995;Grignon et al, 1996) human and mouse tumours. One possible explanation for increased TIMP-1 expression in advanced stages of thyroid carcinoma is that it may represent a secondary event, i.e.…”

Section: Discussionmentioning

confidence: 95%

“…This is supported by the low TIMP-1 expression in both NPA and SW579 thyroid cancer cell lines that are derived from poorly differentiated thyroid carcinomas without stroma contamination. Several studies have demonstrated that increased TIMP-1 or TIMP-2 expression in advanced stages of malignancy derives predominantly from stroma cells rather than from cancer cells themselves (Kossakowska et al, 1991;Visscher et al, 1994b;Zeng et al, 1995;Grignon et al, 1996). In the study of elevated TIMP-1 mRNA levels in non-HodgkinÕs lymphoma, Kossakowska et al (1991) showed by in situ hybridization that TIMP-1 transcripts were not localized to the malignant lymphocytes, but instead were present within stromal cells which account for only 20% of the total cells in each sample.…”

Section: Discussionmentioning

confidence: 99%

“…These investigators found that TIMP-1 mRNA was present predominantly in tumour stroma within spindle fibroblast-like cells. In invasive bladder and breast cancers, elevated TIMP-2 was mostly localized by immunohistochemistry in the tumour stroma around nests of invasive tumour cells (Visscher et al, 1994b;Grignon et al, 1996). In order to determine whether TIMP-1 suppresses thyroid tumour cell invasion through basement membranes, we transfected NPA cells with human TIMP-1 cDNA and isolated clones with high and low TIMP-1 expression.…”

Section: Discussionmentioning

confidence: 99%

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Tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA is elevated in advanced stages of thyroid carcinoma

et al. 1999

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Tumour cell invasion and metastasis is a multistep process that involves the degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) act as negative regulators of MMPs and thus prevent tumour cell invasion and metastasis by preserving extracellular matrix (ECM) integrity. In the present study we examined the expression of one member of TIMPs, TIMP-1, in 39 thyroid tumour specimens and two thyroid carcinoma cell lines (NPA and SW579). We also investigated the effect of high TIMP-1 expression on the invasive potential of NPA cells. Northern blot analysis showed that TIMP-1 mRNA levels correlated directly with tumour aggressiveness: the highest number of TIMP-1 transcripts was found in stages III and IV vs benign goitre ( P < 0.0001). However, TIMP-1 expression was not increased in NPA and SW579 cells, both of which are derived from poorly differentiated thyroid tumours. Immunohistochemical study showed strong TIMP-1 staining in the stroma cells of advanced stages of carcinomas. Overexpression of TIMP-1 by gene transfer resulted in a significant suppression of the malignant phenotype of NPA cells as judged by an in vitro tumour invasion assay. These results suggest that high levels of TIMP-1 transcripts in advanced stages of thyroid carcinoma likely come from stroma rather than thyroid cancer cells, and TIMP-1 may function as a thyroid tumour invasion/metastasis suppressor. © 1999 Cancer Research Campaign

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Enhanced expression of tissue inhibitor of metalloproteinase‐2 (TIMP‐2) in the stroma of breast carcinomas correlates with tumor recurrence

Cited by 154 publications

References 13 publications

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

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

The extracellular matrix produced by bovine corneal endothelial cells contains progelatinase A

Tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA is elevated in advanced stages of thyroid carcinoma

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