Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer

Duffy, M. J.; Bläser, Jörg; Duggan, Catherine; McDermott, Enda; O’Higgins, N.; Jj, Fennelly; Tschesche, Harald

doi:10.1038/bjc.1995.197

Cited by 45 publications

(30 citation statements)

References 23 publications

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“…Previously, using ELISA, we showed a significant correlation between levels of MMP-8 and -9 in breast cancer (Duffy et al, 1995). In the present investigation, we show a significant association between MMP-9 activity and MMP-2 activity (both precursor and active forms).…”

Section: Discussionsupporting

confidence: 70%

Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer

Remacle

Noël²,

Duggan³

et al. 1998

Br J Cancer

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Summary Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in cancer invasion and metastasis. Gelatin zymography was performed on 84 human breast carcinomas and seven normal breast tissues. The precursor form of MMP-2 (72 kDa) was found in 11 (12%) samples, while its two activated forms, i.e. 62 kDa and 59 kDa, were found in three (6%) and 34 (40%) samples respectively. In contrast to MMP-2, most of the samples (52%) contained MMP-9 in its precursor form. Using ELISA, MMP-1 levels were found in 12% of the samples while MMP-3 levels were found in only 2% of the samples. Levels of MMP-2, -3 and -9 correlated inversely with numbers of nodal metastases. Neither MMP-2 nor -9 levels were significantly related to patient outcome. However, patients with high levels of a 50-kDa gelatinase band after zymography had a significantly better survival than patients with low levels. This species was never observed in normal breast tissue.Keywords: breast cancer; gelatinase; stromelysin; interstitial collagenase and matrix metalloproteinaseThe escape of breast cancer cells into neighbouring tissues can lead to the formation of distant metastasis, the most insidious aspect of cancer. It is generally believed that one key element of this metastatic process is the enhanced proteolysis of both basement membrane and stromal extracellular matrix (ECM). Among the proteinases capable of degrading these barriers are the matrix metalloproteinases (MMPs), a family of highly homologous zincdependent endopeptidases (Matrisian, 1990).Based on the protein domain structure, the MMPs can be divided into five main groups (MacDougall and Matrisian, 1995). MMP-7 or matrilysin contains the minimal number of domains, i.e., a predomain, a prodomain and a catalytic domain. MMP-3 (stromelysin-1), MMP-10 (stromelysin-2), MMP-1 1 (stromelysin-3) and MMP-12 (metalloelastase) contain an additional carboxyterminal haemopexin-like domain and represent the second group. The stromelysins have a broad substrate specificity and are capable of degrading many extracellular components, e.g. laminin, fibronectin and proteoglycans. The third group is composed of MMP-1 (interstitial collagenase), MMP-8 (neutrophil collagenase) and MMP-13 (collagenase 3). These MMPs degrade fibrillar collagens and all members of this group have a distinct size and sequence composition in their hinge domain. The most recently described group of MMPs are the membrane-type matrix metalloproteinases. At least some members of this group play a role in the activation of MMP-2 (Sato et al, 1994;Takino et al, 1995). MMP-2 (gelatinase A) and MMP-9 (gelatinase B) account for a separate class based on the presence of a fibronectin-like domain.Gelatinases are able to cleave both the denatured forms of collagen and type IV collagen found in basement membranes. In addition to

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Section: Discussionsupporting

confidence: 70%

Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer

Remacle

Noël²,

Duggan³

et al. 1998

Br J Cancer

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“…Matrix metalloproteinase-8 expression levels correlated with tumour stage and poor prognosis in ovarian cancer (Stadlmann et al, 2003). Levels of MMP-8 and -9 correlated significantly with each other and with TIMP-1 levels, but were not related to tumour size or prognosis in human breast cancer (Duffy et al, 1995). Nothing has been published thus far about SNPs for MMP-8 and cancer, but three MMP-8 promoter haplotypes (MMP-8 -799C4T , MMP-8 þ 17C4G and MMP-8 À381A4G ) have been found to be associated with preterm rupture of membranes in delivery, indicating a functional role on MMP-8 expression .…”

Section: Discussionmentioning

confidence: 87%

Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer

et al. 2006

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Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7 À181A4G . In addition, the genotype distribution of MMP-7 À181A4G was associated with Helicobacter pylori status (w 2 7.8, P ¼ 0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2 303C4T correlated significantly with the WHO classification (w 2 5.9, P ¼ 0.03) and also strongly with tumour-related survival (log rank 11.74, P ¼ 0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2 À1306C4T polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7 À181A4G and TIMP-2 303C4T polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7 À181A4G and TIMP-2 303C4T , may be helpful in identifying gastric cancer patients with a poor clinical outcome.

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“…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). Similarly, high serum level of MMP-2 indicated adverse prognosis in node-positive breast carcinoma (Leppa et al, 2004).…”

Section: Discussionmentioning

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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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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Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer

Cited by 45 publications

References 23 publications

Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer

Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer

Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer

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

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