Role of Mononuclear Cells and Inflammatory Cytokines in Pancreatic Cancer-Related Cachexia
Background and Purpose: The mechanism behind aggressive development of cachexia in patients suffering from pancreatic cancer is not well understood. In this study, we investigated which factors are associated with the cachectic status of the patients and evaluated cachexia-promoting capacity of canc...
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Published in | Clinical cancer research Vol. 11; no. 16; pp. 5802 - 5808 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
15.08.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Background and Purpose: The mechanism behind aggressive development of cachexia in patients suffering from pancreatic cancer is not well understood.
In this study, we investigated which factors are associated with the cachectic status of the patients and evaluated cachexia-promoting
capacity of cancer and inflammatory cells.
Experimental Design: DNA microarray analysis and quantitative reverse transcription-PCR were used to screen for cachexia-associated factors in
pancreatic specimens obtained from noncachectic and cachetic patients diagnosed with pancreatic ductal adenocarcinoma. The
expression pattern of the most prominently altered cachexia-associated factor, interleukin-6 (IL-6), was further analyzed
in patients sera by ELISA, in pancreatic specimens by immunohistochemistry, and in a coculture system by quantitative reverse
transcription-PCR using pancreatic cancer cell lines T3M4 (IL-6 positive) and Panc-1 (IL-6 negative) and peripheral blood
mononuclear cells (PBMC) obtained from donors and noncachectic and cachectic patients.
Results: Among numerous analyzed factors, IL-6 was significantly overexpressed in pancreatic specimens and elevated in serum of cachectic
patients. The coculture system revealed that pancreatic cancer T3M4 cells but not Panc-1 cells were able to stimulate IL-6
exclusively in cachectic PBMC (by 14-fold) and this triggering was reduced by half in the presence of IL-6-neutralizing antibodies.
Conclusion: IL-6 represents a prominent cachexia-associated factor in pancreatic cancer. IL-6 overexpression in cachectic patients is
related to the ability of certain tumors to sensitize PBMC and induce cytokine expression in cachectic PBMC. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-05-0185 |