Dataset Information

Polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13 and MT2A do not contribute to breast, lung and colon cancer risk in polish population.

ABSTRACT: Background:Matrix metalloproteinases (MMPs) and metallothioneins (MTs) are Zinc-related proteins which are involved in processes crucial for carcinogenesis such as angiogenesis, proliferation and apoptosis. Several single nucleotide polymorphisms (SNPs) in MMPs and MTs that affect genes expression have been associated with cancer risk, including breast, lung and colon. Methods:The study group consisted of 648 unselected patients (299 with breast cancer, 199 with lung cancer, 150 with colon cancer) and 648 unaffected individuals. Five SNPs, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A were genotyped and serum zinc (Zn) level was measured. The cancer risk was calculated using multivariable logistic regression with respect to Zn. Results:None of the 5 tested polymorphisms showed a correlation with cancer risk in studied groups, although for MMP-2, MMP-7 and MT2A non-significant differences in genotypes frequencies among cases and controls were observed. Conclusions:Analyses of polymorphisms, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A in relation to serum Zn level did not show significant association with breast, lung and colon cancer risk among polish patients. Further studies are needed to verify this observation.

SUBMITTER: Bialkowska K

PROVIDER: S-EPMC7395404 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Polymorphisms in <i>MMP-1</i>, <i>MMP-2</i>, <i>MMP-7, MMP-13</i> and <i>MT2A</i> do not contribute to breast, lung and colon cancer risk in polish population.

Białkowska Katarzyna K Marciniak Wojciech W Muszyńska Magdalena M Baszuk Piotr P Gupta Satish S Jaworska-Bieniek Katarzyna K Sukiennicki Grzegorz G Durda Katarzyna K Gromowski Tomasz T Lener Marcin M Prajzendanc Karolina K Łukomska Alicja A Cybulski Cezary C Huzarski Tomasz T Gronwald Jacek J Dębniak Tadeusz T Lubiński Jan J Jakubowska Anna A

Hereditary cancer in clinical practice 20200731

<h4>Background</h4>Matrix metalloproteinases (MMPs) and metallothioneins (MTs) are Zinc-related proteins which are involved in processes crucial for carcinogenesis such as angiogenesis, proliferation and apoptosis. Several single nucleotide polymorphisms (SNPs) in MMPs and MTs that affect genes expression have been associated with cancer risk, including breast, lung and colon.<h4>Methods</h4>The study group consisted of 648 unselected patients (299 with breast cancer, 199 with lung cancer, 150 w ...[more]

PMID: 32765800

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Project description:INTRODUCTION: The increased bone degradation in osteolytic metastases depends on stimulation of mature osteoclasts and on continuous differentiation of new pre-osteoclasts. Metalloproteinases (MMP)-13 is expressed in a broad range of primary malignant tumours and it is emerging as a novel biomarker. Recent data suggest a direct role of MMP-13 in dissolving bone matrix complementing the activity of MMP-9 and other enzymes. Tumour-microenvironment interactions alter gene expression in malignant breast tumour cells promoting osteolytic bone metastasis. Gene expression profiles revealed that MMP-13 was among the up-regulated genes in tumour-bone interface and its abrogation reduced bone erosion. The precise mechanism remained not fully understood. Our purpose was to further investigate the mechanistic role of MMP-13 in bone osteolytic lesions. METHODS: MDA-MB-231 breast cancer cells that express MMP-13 were used as a model for in vitro and in vivo experiments. Conditioned media from MDA-MB-231 cells were added to peripheral blood mononuclear cultures to monitor pre-osteoclast differentiation and activation. Bone erosion was evaluated after injection of MMP-13-silenced MDA-MB-231 cells into nude mice femurs. RESULTS: MMP-13 was co-expressed by human breast tumour bone metastases with its activator MT1-MMP. MMP-13 was up-regulated in breast cancer cells after in vitro stimulation with IL-8 and was responsible for increased bone resorption and osteoclastogenesis, both of which were reduced by MMP inhibitors. We hypothesized that MMP-13 might be directly involved in the loop promoting pre-osteoclast differentiation and activity. We obtained further evidence for a direct role of MMP-13 in bone metastasis by a silencing approach: conditioned media from MDA-MB-231 after MMP-13 abrogation or co-cultivation of silenced cells with pre-osteoclast were unable to increase pre-osteoclast differentiation and resorption activity. MMP-13 activated pre-MMP-9 and promoted the cleavage of galectin-3, a suppressor of osteoclastogenesis, thus contributing to pre-osteoclast differentiation. Accordingly, MMP-13 abrogation in tumour cells injected into the femurs of nude mice reduced the differentiation of TRAP positive cells in bone marrow and within the tumour mass as well as bone erosion. CONCLUSIONS: These results indicate that within the inflammatory bone microenvironment MMP-13 production was up-regulated in breast tumour cells leading to increased pre-osteoclast differentiation and their subsequent activation.

Dataset Information

Polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13 and MT2A do not contribute to breast, lung and colon cancer risk in polish population.

Publications

Polymorphisms in <i>MMP-1</i>, <i>MMP-2</i>, <i>MMP-7, MMP-13</i> and <i>MT2A</i> do not contribute to breast, lung and colon cancer risk in polish population.

Similar Datasets

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