Matrix Metalloproteinase-9 -1562T Allele and its Combination with MMP-2 -735 C Allele are Risk Factors for Breast Cancer

Rahimi, Zohreh; Yari, Kheirollah; Rahimi, Ziba

doi:10.7314/apjcp.2015.16.3.1175

Cited by 31 publications

(25 citation statements)

References 22 publications

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“…Thus, it is likely that the substantial inhibition of aggressive human breast tumor growth by anti-ANX A2 mAb treatment is due to inhibition of plasmin-mediated regulation of MMP-9/2 activation. Our observations are consistent with clinical findings wherein both MMP-9 and MMP-2 have been implicated in aggressive breast tumor growth and have been suggested to be significant prognostic indicators of invasive carcinoma and risk factors for breast cancer [37,64,72,77]. Of particular note, MMP-9 is highly expressed in triple negative breast cancer [82] and is associated with distant metastases with shorter progression free survival and overall survival (OS) in patients [83,84].…”

Section: Discussionsupporting

confidence: 89%

“…Previously, it has been reported that MMP-9/2 plays an important role in breast cancer invasion and metastasis, possibly due to induction of neoangiogenesis [75,76]. Indeed, the 1562T allele of MMP-9 and 735C allele of MMP-2 have been shown to be risk factors for breast cancer patients [77]. Consistent with the observations, a study of 270 breast cancer patients demonstrated overexpression of MMP-9/2 with a prognosis for shorter relapse free survival [78].…”

Section: Discussionmentioning

confidence: 99%

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Long-term efficacy and downstream mechanism of anti-annexinA2 monoclonal antibody (anti-ANX A2 mAb) in a pre-clinical model of aggressive human breast cancer

et al. 2016

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There is considerable direct evidence that calcium binding protein ANX A2 is a potential target for treating aggressive breast cancer. The most compelling data are based on the finding of ANX A2 overexpression in aggressive triple negative human breast cancer (TNBC) cell lines and in human breast cancer tissues. Previously, we and others reported a unique role of ANX A2 in cancer invasion, including breast cancer. Moreover, we demonstrated that anti-ANX A2 mAb-mediated immunoneutralization of ANX A2 inhibited invasive human breast cancer growth in a xenograft model. We further evaluated the long-term effects of multiple treatments with anti-ANX A2 mAb and its mechanism of inhibition on human breast tumor growth. We now demonstrate that three treatments with anti-ANX A2 mAb led to significant inhibition of breast tumor growth in immunodeficient mice, and that the anti-tumor response was demonstrable from day 94. After treatment, we followed tumor growth for 172 days and demonstrated 67% inhibition of tumor growth without detectable adverse effects. Biochemical analysis demonstrated that anti-ANX A2 mAb treatment caused significant inhibition of conversion of tissue plasminogen activator (tPA) in the tumor microenvironment. This led to disruption of plasmin generation that consequently inhibited activation of MMP-9 and MMP-2. These results suggest that ANX A2 plays an important role in aggressive breast tumor growth by regulating proteolytic pathways in the tumor microenvironment. ANX A2 may represent a new target for the development of therapeutics for treatment of aggressive breast cancer.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Long-term efficacy and downstream mechanism of anti-annexinA2 monoclonal antibody (anti-ANX A2 mAb) in a pre-clinical model of aggressive human breast cancer

et al. 2016

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“…MMP9 is mainly regulated at the transcriptional level; polymorphisms located in the promoter region have been associated with myocardial infarction, ischaemic stroke, coronary artery disease, lung disorders and a variety of carcinomas (i.e. gastric, breast, urinary) [11,64,66,67]. Short alleles (MMP9 Ã 14) in epithelial cells have shown increased expression activity (two and threefold more) compared to than those with larger repeats (MMP9 Ã 20) [68].…”

Section: Discussionmentioning

confidence: 99%

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

et al. 2020

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Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group ( n = 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included. ALOX5 , LPA , MMP9 and TPO gene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals with clinical manifestations of atherothrombosis than in the healthy group. Once adjusting for population stratification was done, these differences remained. Our results add further evidence on the contribution of ALOX5 , LPA , MMP9 and TPO polymorphisms to atherothrombosis development in the middle-aged group, emphasizing the multiethnic studies in search of gene risk polymorphisms.

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“…17 Studies have demonstrated that degradation of extra cellular matrix and basement membrane by MMPs play an important role in tumorigenesis by modulating cell proliferation, apoptosis, tumor invasion and metastasis. 18 The role played by MMP-9 in the malignancy and the growth of the tumor is an important one. 14 Numerous single-nucleotide polymorphisms (SNPs) have already been identified in the MMP-9 gene, and the most common variant is 1562 C/T (rs 3918242).…”

Section: Discussionmentioning

confidence: 99%

Association between Matrix Metallopeptidase 9 Polymorphism and Breast Cancer Risk

Felizi

Veiga

Filho

et al. 2018

Rev Bras Ginecol Obstet

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Objective Epidemiological studies have shown evidence of the effect of genetic variations in the pathogenesis of breast cancer and have suggested a relationship of the disease with genetic polymorphisms. Matrix metallopeptidase 9 (MMP-9) is a collagenase responsible for the degradation of type IV collagen, the major component of the basement membrane, and other essential extra cellular matrix components, being involved in the tumor cell invasion and metastasis. Our objective was to evaluate the relationship between the MMP-9-1562 C/T polymorphism (rs 3918242) and the risk of developing breast cancer. Methods In this case-control study, the frequency of the MMP-9-1562 C/T polymorphism (rs 3918242) was determined in 148 women with breast cancer and 245 women without the disease. The DNA was extracted from plasma samples, and the gene was amplified by polymerase chain reaction (PCR); the presence of the polymorphism was determined using restriction enzymes. Results After adjusting for confounding variables, we found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio [OR] = 1.159, 95% confidence interval [CI]: 0.6625–1.997, p = 0.5964). We also found no association with more advanced disease, the presence of hormone receptors, human epidermal growth factor receptor 2 (HER2) overexpression, or rate of tumor cell proliferation. Conclusion We did not observe a relationship between MMP-9–1562 C/T polymorphism (rs 3918242) and the occurrence of breast cancer.

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Matrix Metalloproteinase-9 -1562T Allele and its Combination with MMP-2 -735 C Allele are Risk Factors for Breast Cancer

Cited by 31 publications

References 22 publications

Long-term efficacy and downstream mechanism of anti-annexinA2 monoclonal antibody (anti-ANX A2 mAb) in a pre-clinical model of aggressive human breast cancer

Long-term efficacy and downstream mechanism of anti-annexinA2 monoclonal antibody (anti-ANX A2 mAb) in a pre-clinical model of aggressive human breast cancer

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

Association between Matrix Metallopeptidase 9 Polymorphism and Breast Cancer Risk

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