Involvement of the leptin receptor in the immune response in intestinal cancer.
The incidence of colorectal cancers (CRC) may be influenced by environmental factors, including nutrition. The role of peptides regulating food intake in controlling the growth and recurrence of human tumors is controversial. Leptin, a cytokine-like peptide, regulates food intake. We investigated the expression of leptin and its receptor in 171 consecutive patients (78 female and 93 male; 71 years) with CRC. Leptin concentrations in the serum (ELISA) were determined before tumor removal. ObRb was characterized in tumors and normal homologous tissues and culture cells (HT29, HCT116, and HCT116 with a transferred chromosome 3) by using immunocytochemistry, immunohistochemistry, reverse transcription-PCR (RT-PCR), and Western blotting. Microsatellite instability (MSI) phenotype was characterized by immunohistochemistry and pentaplex PCR. mRNAs of cytokines and chemokines were quantified in tumors and in normal homologous tissues (RT-PCR) in 43 patients. Adequate statistical tests, including multivariate analysis adjusted for pathologic tumor-node-metastasis (pTNM), MSI-H, and ObRb phenotypes, were used. Higher expression of ObRb in tumors compared with the homologous normal mucosa, pTNM staging but not leptin serum level, was associated with patients' progression-free survival (PFS). Tumor ObRb phenotype and pTNM were independent predictive factors of PFS. ObRb was more strongly expressed in HCT116 cells than in HCT116-Ch3 cells as well as in MSI-H tumors than in microsatellite stability and potentially associated with efficient cytotoxic antitumoral response as assessed by immunohistochemistry and RT-PCR measurements. We suggest that leptin receptor expression in tumors is involved in adaptive immune response in sporadic colon and rectal tumors likely via MSI-H phenotype orientation.
Aloulou
Nijez
N
Université Paris XII, INSERM and AP-HP, CIC GIT cancer study team, France.
Bastuji-Garin
Sylvie
S
Le Gouvello
Sabine
S
Abolhassani
Mohammad
M
Chaumette
Marie Thérèse
MT
Charachon
Antoine
A
Leroy
Karen
K
Sobhani
Iradj
I
D000368:Aged; D053843:DNA Mismatch Repair; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D020738:Leptin / Q000097:blood; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D054411:Receptors, Leptin / Q000032:analysis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020738:Leptin; D054411:Receptors, Leptin