Fibronectin Affects Transient MMP2 Gene Expression through DNA Demethylation Changes in Non-Invasive Breast Cancer Cell Lines

Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migra...

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Published in:	PloS one Vol. 9; no. 9; p. e105806
Main Authors:	Pereira, Isabela T., Ramos, Edneia A. S., Costa, Erico T., Camargo, Anamaria A., Manica, Graciele C. M., Klassen, Liliane M. B., Chequin, Andressa, Braun-Prado, Karin, de O. Pedrosa, Fábio, Souza, Emanuel M., Costa, Fabricio F., Klassen, Giseli
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 10.09.2014 Public Library of Science (PLoS)
Subjects:	Azacitidine - analogs & derivatives Azacitidine - pharmacology Base Sequence Biochemistry Biology and Life Sciences Blood vessels Breast cancer Breast Neoplasms - pathology Cancer Cancer therapies Cell culture Cell Line, Tumor Cell migration Cell Movement - drug effects Chromatin Collagen (type IV) Degradation Demethylation Deoxyribonucleic acid DNA DNA methylation DNA Methylation - drug effects Epigenetics Epithelial cells Extracellular matrix Fibronectin Fibronectins - pharmacology Gelatinase Gelatinase A Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - genetics Humans Matrix Metalloproteinase 2 - genetics Medical research Metastases Metastasis Molecular biology Molecular Sequence Data Neoplasm Invasiveness Oncology Pathology Promoter Regions, Genetic - genetics Proteins RNA polymerase Solid tumors Stroma Time Factors Tissues Transcriptional Activation - drug effects Tumor cell lines Tumor cells Tumors Brazil United States > US Chicago Illinois
ISSN:	1932-6203, 1932-6203
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Abstract	Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migration. An essential process for metastasis is extracellular matrix (ECM) degradation by metalloproteases (MMPs), which allows tumor cells to invade local tissues and to reach blood vessels. The members of this protein family include gelatinase A, or MMP-2, which is responsible for the degradation of type IV collagen, the most abundant component of the basal membrane, that separates epithelial cells in the stroma. It is known that fibronectin is capable of promoting the expression of MMP-2 in MCF7 breast cancer cells in culture. In addition, it was already shown that the MMP2 gene expression is regulated by epigenetic mechanisms. In this work, we showed that fibronectin was able to induce MMP2 expression by 30% decrease in its promoter methylation. In addition, a histone marker for an open chromatin conformation was significantly increased. These results indicate a new role for fibronectin in the communication between cancer cells and the ECM, promoting epigenetic modifications.
AbstractList	Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migration. An essential process for metastasis is extracellular matrix (ECM) degradation by metalloproteases (MMPs), which allows tumor cells to invade local tissues and to reach blood vessels. The members of this protein family include gelatinase A, or MMP-2, which is responsible for the degradation of type IV collagen, the most abundant component of the basal membrane, that separates epithelial cells in the stroma. It is known that fibronectin is capable of promoting the expression of MMP-2 in MCF7 breast cancer cells in culture. In addition, it was already shown that the MMP2 gene expression is regulated by epigenetic mechanisms. In this work, we showed that fibronectin was able to induce MMP2 expression by 30% decrease in its promoter methylation. In addition, a histone marker for an open chromatin conformation was significantly increased. These results indicate a new role for fibronectin in the communication between cancer cells and the ECM, promoting epigenetic modifications. Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migration. An essential process for metastasis is extracellular matrix (ECM) degradation by metalloproteases (MMPs), which allows tumor cells to invade local tissues and to reach blood vessels. The members of this protein family include gelatinase A, or MMP-2, which is responsible for the degradation of type IV collagen, the most abundant component of the basal membrane, that separates epithelial cells in the stroma. It is known that fibronectin is capable of promoting the expression of MMP-2 in MCF7 breast cancer cells in culture. In addition, it was already shown that the MMP2 gene expression is regulated by epigenetic mechanisms. In this work, we showed that fibronectin was able to induce MMP2 expression by 30% decrease in its promoter methylation. In addition, a histone marker for an open chromatin conformation was significantly increased. These results indicate a new role for fibronectin in the communication between cancer cells and the ECM, promoting epigenetic modifications.Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migration. An essential process for metastasis is extracellular matrix (ECM) degradation by metalloproteases (MMPs), which allows tumor cells to invade local tissues and to reach blood vessels. The members of this protein family include gelatinase A, or MMP-2, which is responsible for the degradation of type IV collagen, the most abundant component of the basal membrane, that separates epithelial cells in the stroma. It is known that fibronectin is capable of promoting the expression of MMP-2 in MCF7 breast cancer cells in culture. In addition, it was already shown that the MMP2 gene expression is regulated by epigenetic mechanisms. In this work, we showed that fibronectin was able to induce MMP2 expression by 30% decrease in its promoter methylation. In addition, a histone marker for an open chromatin conformation was significantly increased. These results indicate a new role for fibronectin in the communication between cancer cells and the ECM, promoting epigenetic modifications.
Author	Camargo, Anamaria A. Klassen, Giseli Klassen, Liliane M. B. Chequin, Andressa Souza, Emanuel M. Costa, Erico T. Manica, Graciele C. M. Costa, Fabricio F. Ramos, Edneia A. S. Braun-Prado, Karin de O. Pedrosa, Fábio Pereira, Isabela T.
AuthorAffiliation	2 Ludwig Institute for Cancer Research (LICR) at Molecular Oncology Center, Sirio-Libanes Hospital, São Paulo, São Paulo, Brazil Florida State University, United States of America 4 Cancer Biology and Epigenomics Program, Ann and Robert Lurie Children’s Hospital of Chicago Research Center and Department of Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, Illinois, United States of America 3 Department of Biochemistry and Molecular Biology, Federal University of Parana, Curitiba, Parana, Brazil 1 Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil
AuthorAffiliation_xml	– name: 3 Department of Biochemistry and Molecular Biology, Federal University of Parana, Curitiba, Parana, Brazil – name: Florida State University, United States of America – name: 1 Department of Basic Pathology, Federal University of Parana, Curitiba, Paraná, Brazil – name: 2 Ludwig Institute for Cancer Research (LICR) at Molecular Oncology Center, Sirio-Libanes Hospital, São Paulo, São Paulo, Brazil – name: 4 Cancer Biology and Epigenomics Program, Ann and Robert Lurie Children’s Hospital of Chicago Research Center and Department of Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, Illinois, United States of America
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: GK ETC FFC. Performed the experiments: EASR ITP GCMM LMBK AC ETC. Analyzed the data: AAC FFC EMS KBP GK. Contributed reagents/materials/analysis tools: AAC EMS FOP. Wrote the paper: ITP EASR ETC FFC FOP GK.
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2005;12(3):128-33
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Snippet	Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they...
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SubjectTerms	Azacitidine - analogs & derivatives Azacitidine - pharmacology Base Sequence Biochemistry Biology and Life Sciences Blood vessels Breast cancer Breast Neoplasms - pathology Cancer Cancer therapies Cell culture Cell Line, Tumor Cell migration Cell Movement - drug effects Chromatin Collagen (type IV) Degradation Demethylation Deoxyribonucleic acid DNA DNA methylation DNA Methylation - drug effects Epigenetics Epithelial cells Extracellular matrix Fibronectin Fibronectins - pharmacology Gelatinase Gelatinase A Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - genetics Humans Matrix Metalloproteinase 2 - genetics Medical research Metastases Metastasis Molecular biology Molecular Sequence Data Neoplasm Invasiveness Oncology Pathology Promoter Regions, Genetic - genetics Proteins RNA polymerase Solid tumors Stroma Time Factors Tissues Transcriptional Activation - drug effects Tumor cell lines Tumor cells Tumors
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Title	Fibronectin Affects Transient MMP2 Gene Expression through DNA Demethylation Changes in Non-Invasive Breast Cancer Cell Lines
URI	https://www.ncbi.nlm.nih.gov/pubmed/25208219 https://www.proquest.com/docview/1561282721 https://www.proquest.com/docview/1561966450 https://pubmed.ncbi.nlm.nih.gov/PMC4160184 https://doaj.org/article/f568db84bdd74ed9a5a6f87942673a62 http://dx.doi.org/10.1371/journal.pone.0105806
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