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DOI10.1073/pnas.2025830118
Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions
Bund T.; Nikitina E.; Chakraborty D.; Ernst C.; Gunst K.; Boneva B.; Tessmer C.; Volk N.; Brobeil A.; Weber A.; Heikenwalder M.; Hausen H.Z.; de Villiers E.-M.
发表日期2021
ISSN00278424
卷号118期号:12
英文摘要Consumption of Eurasian bovine meat and milk has been associated with cancer development, in particular with colorectal cancer (CRC). In addition, zoonotic infectious agents from bovine products were proposed to cause colon cancer (zur Hausen et al., 2009). Bovine meat and milk factors (BMMF) are small episomal DNA molecules frequently isolated from bovine sera and milk products, and recently, also from colon cancer (de Villiers et al., 2019). BMMF are bioactive in human cells and were proposed to induce chronic inflammation in precancerous tissue leading to increased radical formation: for example, reactive oxygen and reactive nitrogen species and elevated levels of DNA mutations in replicating cells, such as cancer progenitor cells (zur Hausen et al., 2018). Mouse monoclonal antibodies against the replication (Rep) protein of H1MSB.1 (BMMF1) were used to analyze BMMF presence in different cohorts of CRC peritumor and tumor tissues and cancer-free individuals by immunohistochemistry and Western blot. BMMF DNA was isolated by laser microdissection from immunohistochemistry-positive tissue regions. We found BMMF Rep protein present specifically in close vicinity of CD68+ macrophages in the interstitial lamina propria adjacent to CRC tissues, suggesting the presence of local chronic inflammation. BMMF1 (modified H1MSB.1) DNA was isolated from the same tissue regions. Rep and CD68+ detection increased significantly in peritumor cancer tissues when compared to tissues of cancer-free individuals. This strengthens previous postulations that BMMF function as indirect carcinogens by inducing chronic inflammation and DNA damage in replicating cells, which represent progress to progenitor cells for adenoma (polyps) formation and cancer. © 2021 National Academy of Sciences. All rights reserved.
英文关键词BMMF | antigen | chronic inflammation | colon cancer
语种英语
scopus关键词bovine meat and milk factors; CD68 antigen; DNA; monoclonal antibody; replication factor A; unclassified drug; antigen detection; antigen expression; Article; cancer tissue; cell division; cell interaction; chronic inflammation; clinical article; cohort analysis; colon carcinogenesis; colonic lamina propria; colorectal cancer; controlled study; DNA damage; DNA isolation; human; human cell; human tissue; immunohistochemistry; laser microdissection; macrophage; priority journal; stem cell; Western blotting
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180133
作者单位Division of Episomal-Persistent DNA in Cancer and Chronic Diseases, German Cancer Research Center, Heidelberg, 69120, Germany; Monoclonal Antibody Unit, German Cancer Research Center, Heidelberg, 69120, Germany; Institute of Pathology Heidelberg, University Hospital Heidelberg, Heidelberg, 69120, Germany; Tumor Bank Unit, Tissue Bank of the National Center for Tumor Diseases, Heidelberg, 69120, Germany; Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zürich, Zürich, 8091, Switzerland; Institute of Molecular Cancer Research, University of Zürich, Zürich, 8091, Switzerland; Division of Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg, 69120, Germany
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Bund T.,Nikitina E.,Chakraborty D.,et al. Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions[J],2021,118(12).
APA Bund T..,Nikitina E..,Chakraborty D..,Ernst C..,Gunst K..,...&de Villiers E.-M..(2021).Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA Bund T.,et al."Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).
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