Document Detail


Leptin receptor-related immune response in colorectal tumors: the role of colonocytes and interleukin-8.
MedLine Citation:
PMID:  19010917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have shown that ObRb, the leptin receptor, is overexpressed in colorectal cancer cells, and that this may influence the patients' outcome. We investigated colonocytes as leptin targets and characterized their pivotal role in antitumor immune response. Cytokine and chemokine mRNAs in HT29 cells were measured by targeted arrays. In vitro, normal colonocytes and human colon cancer cells (HT29, Caco-2, SW480, and HCT116) were used to investigate ObRb transduction system and cytokine releases. Animal colonocytes and CD8 splenocytes and human HT29, HCT116, and CD8(+) cells from blood donors were used to investigate the lymphocyte response to the colonocytes when stimulated by leptin. Leptin-induced cytokine releases in the normal colonic mucosa and tumor growth and cytokine releases within tumors in vivo were measured in male rats and nude mice, respectively. Statistical analysis was done by Fisher's exact and Mann-Whitney U tests. Various cytokines and their receptors were produced in normal and tumoral colonocytes in response to leptin by increasing nuclear factor-kappaB activation. Interleukin-8 (IL-8) was the main cytokine produced in vitro. The levels of IL-8 and its receptor, CXCR1, were higher in tumors than in homologous normal mucosa. Systemic leptin enhanced the proinflammatory cytokines in normal colonocytes and in HT29 xenografted tumor colonocytes. Colonocyte-derived products after leptin treatment stimulated perforin and granzyme B expressions in normal CD8(+) T cells in vitro. Leptin triggers an inflammatory response in tumor tissue by directly stimulating colonocytes, which can recruit T cytotoxic cells in the tumor microenvironment.
Authors:
Mohammad Abolhassani; Nijez Aloulou; Marie Thérèse Chaumette; Thomas Aparicio; Nadine Martin-Garcia; Hicham Mansour; Sabine Le Gouvello; Jean Charles Delchier; Iradj Sobhani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  68     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2008-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9423-32     Citation Subset:  IM    
Affiliation:
Université Paris Est (XII) and AP-HP, GIT Cancer Study Team INSERM-CIC, France.
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MeSH Terms
Descriptor/Qualifier:
Aged
Animals
Cell Line, Tumor
Colon / cytology
Colorectal Neoplasms / immunology*
Enterocytes / physiology*
Female
Humans
Interleukin-8 / physiology*
Leptin / pharmacology
Male
Mice
Mice, Inbred BALB C
Middle Aged
NF-kappa B / metabolism
Rats
Receptors, Leptin / physiology*
Chemical
Reg. No./Substance:
0/Interleukin-8; 0/Leptin; 0/NF-kappa B; 0/Receptors, Leptin

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