Tissue inhibitor of metalloproteinases-1 in breast cancer

Würtz, Sidse Ørnbjerg; Schrohl, A-S; Sørensen, Nanna Møller; Lademann, Ulrik; Christensen, Ib Jarle; Mouridsen, Henning T.; Brünner, Nils

doi:10.1677/erc.1.00719

Cited by 100 publications

(73 citation statements)

References 69 publications

(58 reference statements)

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“…Furthermore, by cleaving proapoptotic factors, MMPs produce a more aggressive phenotype via generation of apoptotic resistant cells [20]. MMPs also regulate cancer-related angiogenesis, positively through their ability to mobilize or activate proangiogenic factors [21], and negatively via generation of angiogenesis inhibitors, such as angiostatin and endostatin, cleaved from large protein precursors [22] On the other hand, it is now accepted that TIMPs are multifactorial proteins also involved in the induction of proliferation and the inhibition of apoptosis [23,24].…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas

Casar

González

Delgado

et al. 2009

Breast Cancer Res Treat

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An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 5,000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed at the center of the tumor and the invasive front. Immunostaining for MMPs/TIMPs by fibroblasts was evaluated. To identify specific groups of tumors with distinct expression profiles, the data obtained from both fibroblast populations were analyzed by unsupervised hierarchical cluster analysis. Intratumor stromal fibroblasts more frequently showed expression of MMP-2, -7, and -14, and TIMP-3, but less frequently of MMP-9 than fibroblasts at the invasive front. Multivariate analysis showed that a high profile of MMPs and TIMPs staining in both fibroblast populations was the most potent predictor factor of distant metastases, whereas a low staining profile in fibroblasts was associated with a low risk of metastases.

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Section: Introductionmentioning

confidence: 99%

Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas

Casar

González

Delgado

et al. 2009

Breast Cancer Res Treat

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“…Matrix metalloproteinases may also regulate cancer/related angiogenesis, both positively through their ability to mobilise or activate proangiogenic factors (Stetler-Stevenson, 1999) and negatively via generation of angiogenesis inhibitors, such as angiostatin and endostatin, cleaved from large protein precursors (Cornelius et al, 1998). In addition, it is now assumed that TIMPs are multifactorial proteins also involved in the induction of proliferation and the inhibition of apoptosis (Jiang et al, 2002;Wurtz et al, 2005).…”

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confidence: 99%

Study of matrix metalloproteinases and their inhibitors in breast cancer

et al. 2007

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An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.

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“…Currently, four different TIMPs are known to exist: TIMPs 1, 2, 3 and 4. However, it is now assumed that TIMPs are multifactorial proteins that are also involved in the induction of proliferation and inhibition of apoptosis (Wurtz et al, 2005).The expression in prostate cancer of several MMPs and TIMPs, such as MMP-2, -7, -9, -13 and -14, TIMP-1, -2 and -3, has been recently reported ( The objectives of this study were to evaluate the expression and clinical relevance of several MMPs and TIMPs of previously recognised biological importance in prostate carcinomas, using the tissue array (TA) technique. This technique has allowed us the processing of a large number of tissue specimens for a wide range of protein determinations.…”

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confidence: 99%

“…If TIMPs inhibit MMPs in vivo, it should be expected that high levels of these inhibitors would prevent tumour progression and thus be related with low aggressiveness of tumours. However, TIMPs are multifunctional proteins that, in addition to its MMP-inhibitory effect, also show distinct tumourstimulatory functions involved in the induction of proliferation and inhibition of apoptosis (Jiang et al, 2002;Wurtz et al, 2005).In this study, we also investigated the possible relationship between each one of MMPs or TIMPs expressions and clinical outcome, such as PSA-defined recurrence after radical prostatectomy in our studied population. Our results showed that the global expression of MMP-11 and -13 by prostate carcinomas correlated with higher incidence rate of biochemical relapse.…”

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Study of matrix metalloproteinases and their inhibitors in prostate cancer

Escaff

Fernández²,

González

et al. 2010

Br J Cancer

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BACKGROUND: Extracellular matrix metalloproteases (MMPs) have raised an extraordinary interest in cancer research because of their potential role in basal membrane and extracellular matrix degradation, consequently facilitating tumour invasion and metastases development. METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs 1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors, TIMPs 1, 2 and 3. More than 2600 determinations on cancer specimens from 133 patients with clinically localised prostate carcinoma, 20 patients with prostatic intraepithelial neoplasia and 50 patients with benign prostate hyperplasia and controls, were performed. RESULTS: When compared with benign pathologies, prostate carcinomas had higher expression of all MMPs and TIMPs. Dendogram shows a first-order division of tumours into two distinct MMPs/TIMPs molecular profiles, one of them with high MMPs/TIMs expression profile (n ¼ 70; 52.6%). Tumours with high expression of MMP-11 or -13, or cluster thereof, were significantly associated with higher probability of biochemical recurrence. The prevalence of prostate cancer is so high that it could be considered as a normal age-related phenomenon (Hughes et al, 2005). Several published autopsy series have shown that up to one-third of men between the ages of 30 and 40 years harbour histological evidence of prostate carcinoma (Sakr et al, 1994).A significant minority of patients undergoing radical prostatectomy for clinical organ-confined disease will ultimately be found to have pathological evidence of spread outside the prostate. Although these patients may be expected to have progression and survival rates comparable to those of patients with clinical advanced clinical disease, as defined by grade and serum prostatespecific antigen (PSA) level, those men who present with clinical stage T3 are likely to have greater tumour volume, higher grade and increased likelihood of regional spread. Currently, the majority of men undergoing prostatectomy for pathologically advanced disease are categorised as high risk on the basis of serum PSA value or biopsy Gleason score. Nevertheless, there is some overlap in the groups of men undergoing radical prostatectomy for clinical stage T3 and for pathological stage T3 (Meng and Carrol, 2007).Despite recent improvement in diagnostic and therapeutic techniques, the survival rate of prostate cancer patients remains poor due to post-treatment recurrence disease. Despite all the recent efforts in the identification of molecular mechanisms involved in the progression of prostate cancer, tumour progression in the prostatic compartment, as well as in the metastasis compartment, is poorly understood (Logothetis and Lin, 2005). These pitfalls underscore the need for new risk markers that allow the early detection of carcinogenesis and, therefore, of cancer relapse.Degradation of the stromal connective tissue and basement membrane components are key elements in tumour invasion and metastasis. This is particularly true wi...

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Tissue inhibitor of metalloproteinases-1 in breast cancer

Cited by 100 publications

References 69 publications

Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas

Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas

Study of matrix metalloproteinases and their inhibitors in breast cancer

Study of matrix metalloproteinases and their inhibitors in prostate cancer

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