Enhanced expression and activation of major matrix metalloproteinases in distinct topographic areas of invasive breast carcinomas

Bachmeier, Beatrice E.; Rohrbach, Helmut; Waal, J. De; Jochum, Marianne; Nerlich, Andreas

doi:10.3892/ijo.26.5.1203

Cited by 12 publications

(19 citation statements)

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“…However, MMP-9 is expressed at very low levels in the breast cancer cells used in our study and metastasis formation crucially relies on collagen I degradation operated by MMP-1 expressed by MDA-MB-231 cells and not by the gelatinase MMP-9 that cannot degrade the ECM compound native collagen and therefore promotes only local tumor growth. Mammary carcinoma cells show highest levels of MMP expression in sparse cultures or at the tumor periphery, where cells grow in a less compact pattern and three-dimensional cultures of these cells have an elevated proteolytic activity in regions of low cellular density [67][68][69]. Well in line with our previous observations, we show that the effects of Curcumin on cell growth and viability are more pronounced in subconfluent cells and could thus have a particular impact on single metastasizing cells.…”

Section: Discussionsupporting

confidence: 79%

The Chemopreventive Polyphenol Curcumin Prevents Hematogenous Breast Cancer Metastases in Immunodeficient Mice

Bachmeier

Nerlich

Iancu

et al. 2007

Cell Physiol Biochem

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161

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Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA-MB-231 cells in correlation with reduced activation of the survival pathway NFκB, as a consequence of diminished ΙκΒ and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NFκB activity and transcriptional downregulation of AP-1. NFκB/p65 silencing is sufficient to downregulate cjun and MMP expression. Reduced NFκB/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NFκB/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible.

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Section: Discussionsupporting

confidence: 79%

The Chemopreventive Polyphenol Curcumin Prevents Hematogenous Breast Cancer Metastases in Immunodeficient Mice

Bachmeier

Nerlich

Iancu

et al. 2007

Cell Physiol Biochem

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191

161

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“…Thus, the only reason for women in the control group to have a hysterectomy was cervical pathology. In both groups, the endometrial dating was classified into proliferative (days 1-13), early secretory (days [14][15][16][17][18][19], midsecretory (days 20-23), and late secretory (days 24-28) phases by endometrial histology, according to the study by Noyes et al (19). The clinical characteristics and menstrual phases of each group are summarized in Table 1.…”

Section: Tissue Sections For Immunohistochemistrymentioning

confidence: 99%

“…Increased MMP activity has been implicated in endometrial invasion and implantation in endometriosis, as well as tumor-cell invasion or growth (14,15). In addition, MMP-2 or -9 expression was shown to be higher in the eutopic and ectopic endometrial tissues of adenomyosis patients, compared with healthy tissues (16,17), suggesting that MMPs might play a crucial role in the development of adenomyosis.…”

mentioning

confidence: 98%

Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells

Kim

Ihm

et al. 2015

Fertility and Sterility

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“…triosis [5,6] . Although 18 members of the MMP family have been described [7] , the gelatinases MMP-9, formerly known as gelatinase B, as well as MMP-2 have been most consistently detected in malignant tissues and are associated with tumor aggressiveness and metastatic potential [8][9][10] .…”

mentioning

confidence: 99%

Matrix Metalloproteinase-2 and -9 Expression Correlated with Angiogenesis in Human Adenomyosis

Tian

2006

Gynecol Obstet Invest

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Background: Adenomyosis is an important cause of dysmenorrhea and infertility for women all over the world, however, the pathogenesis has not been completely elucidated. The purpose of the study was to investigate the role of matrix metalloproteinases (MMPs) and their relation to angiogenesis in human adenomyosis. Methods: Adenomyotic endometrial specimens were removed by hysterectomy from 68 women with adenomyosis. The control group consisted of 26 normal endometrial specimens. Immunohistochemistry was used to demonstrate expression of MMP-2, -9, vascular endothelial growth factor (VEGF) and microvessel density (MVD). Staining intensity was analyzed by computerized image analysis system. Results: In both eutopic and ectopic endometrium of adenomyosis, the expression of MMP-2, -9 as well as VEGF was significantly greater than in normal endometrium (p < 0.05). MVD was higher in ectopic endometrium than eutopic endometrium with or without adenomyosis (p < 0.05). In adenomyosis, a positive correlation was observed between VEGF expression and MMP-2 (p < 0.001, r = 0.583) as well as MMP-9 expression (p = 0.002,r = 0.490). A positive correlation was also found between MVD and MMP-2 (p < 0.001,r = 0.589) or MMP-9 expression (p < 0.001,r = 0.589). Conclusion: Our results indicate that the elevation of MMP-2, -9 expression may have an important role in the development of adenomyosis, probably through contributing to invasion of endometrial tissues into the myometrium and angiogenesis in adenomyotic implants.

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Enhanced expression and activation of major matrix metalloproteinases in distinct topographic areas of invasive breast carcinomas

Cited by 12 publications

References 0 publications

The Chemopreventive Polyphenol Curcumin Prevents Hematogenous Breast Cancer Metastases in Immunodeficient Mice

The Chemopreventive Polyphenol Curcumin Prevents Hematogenous Breast Cancer Metastases in Immunodeficient Mice

Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells

Matrix Metalloproteinase-2 and -9 Expression Correlated with Angiogenesis in Human Adenomyosis

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