Metalloproteinases: role in breast carcinogenesis, invasion and metastasis

Duffy, Michael J.; Maguire, Teresa; Hill, Arnold D.; McDermott, Enda; O’Higgins, N.

doi:10.1186/bcr65

Cited by 533 publications

(441 citation statements)

References 44 publications

(64 reference statements)

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“…Dotted lines indicate the upper limit of healthy controls (95th percentiles); the percentages represent the proportion of patients with values above the upper limit of healthy controls at baseline and at follow-up. Duffy et al, 2000). MMP-9 has been found to be associated with poor prognosis and metastatic potential of breast carcinoma (Duffy et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Increased levels of MMPs have been found associated with basement membrane invasion, which plays an important role in metastasis formation (Kalebic et al, 1983;Stetler-Stevenson, 1994, 1995Kleiner and Stetler-Stevenson, 1999). The activity of MMPs is regulated by tissue inhibitors (TIMPs) (Chenard et al, 1996;Duffy et al, 2000;Hirvonen et al, 2003). Among the different MMPs, it has been shown that increased expression of MMP-2 was associated with early relapse and short survival (TalvensaariMattila et al, 1998;Talvensaari-Mattila et al, 1999).…”

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confidence: 99%

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Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Voorzanger-Rousselot¹,

Juillet²,

Mareau³

et al. 2006

Br J Cancer

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Complex biological pathways including angiogenesis, invasion, osteoclastic activation and bone matrix degradation are involved in the formation of bone metastasis (BM). The aim of our study was to investigate the cross-sectional and longitudinal associations of a panel of 12 serum biochemical markers reflecting biological pathways underlying BM development. In a cross-sectional study, we investigated 29 patients with primary breast carcinoma without BM (BC/BMÀ), 28 patients with breast carcinoma and BM (BC/ BM þ ) and 15 healthy women. In longitudinal analyses, we investigated 34 patients for whom serum was obtained a two different time points: at the time of primary BC diagnosis and after a median time of 3 years. During this follow-up, 15 patients developed BM, whereas the other 19 remained free of BM. In patients who developed BM, the second samples were obtained before BM was documented by bone scan. The cross-sectional analyses have shown all biochemical markers to be significantly elevated in patients with BM, when compared to the patients without BM and healthy controls, except TGFb1 that was significantly decreased. Multivariable analyses showed that only the bone resorption markers TRACP 5b, CTX and ICTP, and the marker of angiogenesis VEGF were independently associated with BM. Those markers correctly distinguished 85% of BC patients with or without BM from normal individuals. Longitudinal analyses showed that patients with primary BC who developed BM during follow-up had higher levels of TRACP5b ( þ 95%, P ¼ 0.08) at the time of primary diagnosis, those patients had also a higher increases of ICTP (P ¼ 0.006), MMP-7 (P ¼ 0.004) and TIMP-1 (P ¼ 0.017) during follow-up than patients who did not progress toward bone metastasis. This study provides evidence of increase and interrelationship of circulating markers of angiogenesis, invasion and bone resorption in patients with BC with and without BM. Markers of bone resorption have the highest independent diagnostic value for detecting and potentially predicting BM in breast carcinoma patients. Bone is one of the most common sites of metastasis for certain types of tumours, especially prostate, breast and lung carcinoma (Mundy, 2002). Breast cancer progression to bone is a defining feature of a highly malignant tumour and the major cause of cancer-treatment failure. Early detection of bone metastasis is critical for clinical management and accurate staging of tumours. Currently there is no a simple way to reliably detect and predict which patients will develop bone metastasis. The detection of bone metastases relies on imaging technology, but novel approaches based on biomarker assessments are under intense investigation. Increasing body of data suggests that metastatic dissemination is site specific (Horak and Steeg, 2005) and that distinct molecular factors regulate bone metastasis formation (Yin et al, 2005). A multifactorial and multistep process of bone metastasis formation involves several biological mechanisms including angiogenesis, invasion through...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Voorzanger-Rousselot¹,

Juillet²,

Mareau³

et al. 2006

Br J Cancer

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“…Immunoreactivity for MMP-2 was correlated significantly with Masaoka clinical stage, and MMP-2 expression was correlated with the degree of malignant behavior of the thymoma and may be an indicator for distinguishing invasive thymoma from noninvasive thymoma. MMP-2 protein reportedly is correlated with poor prognostic variables in a variety of malignancies, such as breast, 15,16 lung, 17,18 stomach, 19 and head and neck carcinomas. 20 It was long been believed that TIMPs suppressed tumor invasion by inhibiting MMPs in experimental and clinical studies.…”

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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“…Gelatinases A (MMP-2) and B (MMP-9) can both degrade type IV collagen of basement membranes, the first barrier for cancer invasion. Consistent with their role in breast cancer progression, high levels of MMP-2 have been found to correlate with a poor prognosis in breast cancer patients (Talvensaari-Mattila et al, 1998;Duffy et al, 2000). These MMPs may also play a role in tumour vascularisation.…”

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confidence: 91%

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

et al. 2004

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The overexpression of angiogenic factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and insulin-like growth factors (IGFs) plays a role in the migration and proliferation of endothelial cells in many cancers. Consequently, we investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists on the expression of these angiogenic factors, the activities of matrix metalloproteinases (MMPs)-2 and -9, as well as the vascular density in MDA-MB-435 human oestrogenindependent breast cancers. Nude mice bearing orthotopic xenografts of MDA-MB-435 breast cancers were treated with bombesin/ GRP antagonists for 6 weeks. Daily administration of 20 mg of RC-3095 or 10 mg of RC-3940-II significantly decreased the weight of MDA-MB-435 cancers by 44 and 53%, respectively. The inhibition of tumour growth was associated with a substantial reduction in the expression of mRNA and protein levels of basic fibroblast growth factor (bFGF), IGF-II and VEGF-A in the tumours. Both bombesin/GRP antagonists significantly decreased the vessel density of the tumours by about 37%, as shown by immunohistochemical detection of vessels on tumour slides. Gelatinolytic activities, detected by zymography, revealed a 33 -46% reduction in MMP-9 activity after the treatment with either antagonist. In vitro studies revealed that MDA-MB-435 cells secrete bFGF, IGF-II and VEGF-A, and the secretion of these factors is inhibited by RC-3095 and RC-3940-II. This study demonstrates the antiangiogenic effect of bombesin/GRP antagonists RC-3095 and RC-3940-II, and underscores their possible therapeutic application for treatment of breast cancers.

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Metalloproteinases: role in breast carcinogenesis, invasion and metastasis

Cited by 533 publications

References 44 publications

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

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

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

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