Heme oxygenase-1 promotes tumor progression and metastasis of colorectal carcinoma cells by inhibiting antitumor immunity

• Published in: Oncotarget Vol. 6; no. 23; pp. 19792 - 19806
• Main Authors: Seo, Geom Seog, Jiang, Wen-Yi, Chi, Jin Hua, Jin, Hao, Park, Won-Chul, Sohn, Dong Hwan, Park, Pil-Hoon, Lee, Sung Hee
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 14.08.2015
• Subjects: Animals; Caco-2 Cells; Cell Adhesion; Chemokine CXCL10 - metabolism; Chemotaxis, Leukocyte; Coculture Techniques; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Cytotoxicity, Immunologic; Disease Progression; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; HT29 Cells; Humans; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Lymphocytes - immunology; Lymphocytes - metabolism; Male; Mice, Inbred BALB C; Neoplasm Metastasis; Receptors, CXCR3 - metabolism; Research Paper; RNA Interference; RNA Stability; RNA, Messenger - metabolism; Signal Transduction; Transfection; Tristetraprolin - metabolism; Tumor Escape; CXCL10; colorectal carcinoma cell; HO-1; ICAM-1; antitumor immunity
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.4075

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.