Abstract:
:That tumors cause changes in surrounding tissues is well documented, but whether they also affect distant tissues is uncertain. Such knowledge may be important in understanding the relationship between cancer and overall patient health. To address this question, we examined tissues distant to sites of implanted tumors for genomic damage using cohorts of C57BL/6 and BALB/c mice with early-stage subcutaneous syngeneic grafts, specifically, B16 melanoma, MO5076 sarcoma, and COLON26 carcinoma. Here we report that levels of two serious types of DNA damage, double-strand breaks (DSBs) measured by γ-H2AX focus formation and oxidatively induced non-DSB clustered DNA lesions (OCDLs), were elevated in tissues distant from the tumor site in tumor-bearing mice compared with their age- and sex-matched controls. Most affected were crypts in the gastrointestinal tract organs and skin, both highly proliferative tissues. Further investigation revealed that, compared with controls, tumor-bearing mice contained elevated amounts of activated macrophages in the distant gastrointestinal tissues, as well as elevated serum levels of several cytokines. One of these cytokines, CCL2/MCP-1, has been linked to several inflammation-related conditions and macrophage recruitment, and strikingly, CCL2-deficient mice lacked increased levels of DSBs and OCDLs in tissues distant from implanted tumors. Thus, this study is unique in being a direct demonstration that the presence of a tumor may induce a chronic inflammatory response in vivo, leading to increased systemic levels of DNA damage. Importantly, these findings suggest that tumors may have more profound effects on their hosts than heretofore expected.
journal_name
Proc Natl Acad Sci U S Aauthors
Redon CE,Dickey JS,Nakamura AJ,Kareva IG,Naf D,Nowsheen S,Kryston TB,Bonner WM,Georgakilas AG,Sedelnikova OAdoi
10.1073/pnas.1008260107subject
Has Abstractpub_date
2010-10-19 00:00:00pages
17992-7issue
42eissn
0027-8424issn
1091-6490pii
1008260107journal_volume
107pub_type
杂志文章abstract::Receptors for platelet-derived growth factor (PDGF) have previously only been found on cells of mesenchymal and glial origin. This study shows PDGF receptors on an anaplastic thyroid carcinoma cell line, C 643, that was found to express thyroglobulin mRNA, confirming its origin from thyroid epithelium. Northern blot a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.23.9302
更新日期:1988-12-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.87.13.5168
更新日期:1990-07-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.3.1272
更新日期:1977-03-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.95.26.15571
更新日期:1998-12-22 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.76.7.3445
更新日期:1979-07-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1991-04-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1986-07-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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pub_type: 杂志文章
doi:10.1073/pnas.85.16.5804
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1998-08-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1992-12-15 00:00:00
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pub_type: 杂志文章
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更新日期:1984-08-01 00:00:00
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更新日期:2012-01-17 00:00:00
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更新日期:2014-09-02 00:00:00