title: Chemokine CXCL16 suppresses liver metastasis of colorectal cancer via             augmentation of tumor-infiltrating natural killer T cells in a murine model.
abstract: Colorectal cancer (CRC) is a typical lifestyle-related disease, and it metastasizes             mostly to the liver. It is important to understand the molecular mechanisms of             CRC metastasis in order to design new and effective treatments for CRC patients.             Chemokines are known to have antitumor effects as their chemoattractant properties             stimulate the accumulation of infiltrating immune cells (TILs) in tumors. Chemokine             (C-X-C motif) ligand 16 (CXCL16), also known as SR-PSOX, is a unique membrane-bound             chemokine that induces the expression of its specific receptor CXCR6. We previously             reported that the expression of CXCL16 by cancer cells enhances the recruitment             of TILs, thereby improving the prognosis of CRC. It has since been reported that             CXCL16/CXCR6 expression is involved in the metastasis of various types of cancer.             However, there is no report of the association between CXCL16 expression and liver             metastasis in CRC. In this study, we investigated the role of cancer-derived CXCL16             and the possibility of gene therapy using CXCL16. Therefore, we examined the metastasis             of colon 38 SL4 cells to the liver in an experimental model. Following injection             of cancer cells into the intraportal vein, CXCL16-expressing CRC cells drastically             inhibited liver metastasis. We also found that CD8 T cells and natural killer T             (NKT) cells, known as CXCR6-expressing cells, increased in CXCL16-expressing metastatic             tissue. Collectively, the inhibitory effect on metastasis to the liver by CXCL16             was observed in NKT cell-depleted mice but not in CD8 T cell-depleted mice. These             results demonstrate the inhibitory effect of CXCL16 on liver metastasis via NKT             cells in CRC.
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Kee
authors.forename: Aya
authors.initials: A
authors.lastname: Ito
authors.forename: Shozo
authors.initials: S
authors.lastname: Hojo
authors.forename: Isaya
authors.initials: I
authors.lastname: Hashimoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Shibahara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D055611:Natural Killer T-Cells / Q000276:immunology*; D009368:Neoplasm Transplantation
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse