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

Title
Heme oxygenase-1 promotes tumor progression and metastasis of colorectal carcinoma cells by inhibiting antitumor immunity
Author(s)
박필훈이성희[이성희]서검석[서검석]손동환[손동환]박원철[박원철]Wen-Yi Jiang[Wen-Yi Jiang]Jin Hua Chi[Jin Hua Chi]Hao Jin[Hao Jin]
Keywords
INTERCELLULAR-ADHESION MOLECULE-1; PHORBOL-MYRISTATE ACETATE; REGULATORY T-CELLS; GENE-EXPRESSION; UP-REGULATION; MEDIATED CYTOTOXICITY; PHOTODYNAMIC THERAPY; ENDOTHELIAL-CELLS; ICAM-1 EXPRESSION; CANCER CELLS
Issue Date
201508
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET, v.6, no.23, pp.19792 - 19806
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.
URI
http://hdl.handle.net/YU.REPOSITORY/31294
ISSN
1949-2553
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약학대학 > 약학부 > Articles
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