title: Heme oxygenase-1 promotes tumor progression and metastasis of colorectal carcinoma cells by inhibiting antitumor immunity.
abstract: Heme oxygenase-1 (HO-1) is upregulated in colorectal carcinoma (CRC) cells. However, the role of HO-1 in the metastatic potential of CRC remains to be elucidated. In this study, we investigated the potential of HO-1 to control the antitumor immunity of CRC. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the immune surveillance system. Hemin-induced HO-1 expression suppressed the expression of ICAM-1 in human CRC cells. HO-1 regulated ICAM-1 expression via tristetraprolin, an mRNA-binding protein, at the posttranscriptional level in CRC cells. The upregulated HO-1 expression in CRC cells markedly decreased the adhesion of peripheral blood mononuclear lymphocytes (PBMLs) to CRC cells and PBML-mediated cytotoxicity against CRC cells. Production of CXCL10, an effector T cell-recruiting chemokine, was significantly reduced by the increased HO-1 expression. The expression of the CXCL10 receptor, CXCR3, decreased significantly in PBMLs that adhered to CRC cells. HO-1 expression correlated negatively, although nonsignificantly, with ICAM-1 and CXCL10 expression in xenograft tumors. Taken together, our data suggest that HO-1 expression is functionally linked to the mediation of tumor progression and metastasis of CRC cells by inhibiting antitumor immunity.
authors.affiliation: Digestive Disease Research Institute, Wonkwang University College of Medicine, Jeonbuk, Republic of Korea.
authors.forename: Geom Seog
authors.initials: GS
authors.lastname: Seo
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Republic of Korea.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Jiang
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Republic of Korea.
authors.forename: Jin Hua
authors.initials: JH
authors.lastname: Chi
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Republic of Korea.
authors.forename: Hao
authors.initials: H
authors.lastname: Jin
authors.affiliation: Digestive Disease Research Institute, Wonkwang University College of Medicine, Jeonbuk, Republic of Korea.
authors.forename: Won-Chul
authors.initials: WC
authors.lastname: Park
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Republic of Korea.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Sohn
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongbuk, Republic of Korea.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Republic of Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002448:Cell Adhesion; D054357:Chemokine CXCL10 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D051816:Tristetraprolin / Q000378:metabolism; D019139:Tumor Escape
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; C573420:ICAM1 protein, human; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D018799:Intercellular Adhesion Molecule-1; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: CXCL10; HO-1; ICAM-1; antitumor immunity; colorectal carcinoma cell