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.
Highlights
Colorectal carcinoma (CRC) contributes to the overall cancer mortality [1]
Because Intercellular adhesion molecule-1 (ICAM-1) has been reported to play an important role in the interaction between tumor cells and host cytotoxic effector cells [15,16,17], we evaluated the effects of Heme oxygenase-1 (HO-1) on the adhesion of peripheral blood mononuclear lymphocytes (PBMLs) to CRC cells
The objective of our study was to identify the role of HO-1 in the progression and metastatic potential of CRC cells
Summary
Colorectal carcinoma (CRC) contributes to the overall cancer mortality [1]. Mortality can be prevented by surgical resection before tumor cell dissemination, CRC progression and metastases are the main causes of death [2]. Elucidation of the molecular pathways involved in tumor progression and metastasis may yield novel therapeutic approaches. The results of studies into the role of HO-1 in tumor progression remain controversial. The proangiogenic action of HO-1 may further support tumor progression [11, 12]. By con trast, some studies have suggested that HO-1 induction contributes to a lower risk of lymph node metastasis in human colorectal and oral carcinoma [13]. The role of HO-1 in the metastatic potential of CRC cells remains to be elucidated fully
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