Heme oxygenase-1 promotes tumor progression and metastasis of colorectal carcinoma cells by inhibiting antitumor immunity
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Geom Seog Seo1, Wen-Yi Jiang2, Jin Hua Chi2, Hao Jin2, Won-Chul Park1, Dong Hwan Sohn2, Pil-Hoon Park3, Sung Hee Lee2
1Digestive Disease Research Institute, Wonkwang University College of Medicine, Jeonbuk, Republic of Korea
2Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Republic of Korea
3College of Pharmacy, Yeungnam University, Gyeongbuk, Republic of Korea
Sung Hee Lee, e-mail: [email protected]
Keywords: HO-1, colorectal carcinoma cell, antitumor immunity, ICAM-1, CXCL10
Received: March 03, 2015 Accepted: May 18, 2015 Published: May 28, 2015
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.
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