title: The expression, function and targeting of haem oxygenase-1 in cancer.
abstract: Haem oxygenase-1 (HO-1) catalyses the rate-limiting step in haem degradation. All three metabolites resulting from haem degradation (carbon monoxide (CO), biliverdin and free iron) have anti-inflammatory and anti-apoptotic properties. HO-1 is a stress-inducible enzyme found extensively expressed in a vast variety of both human and murine cancers, where it serves as an essential survival molecule by modulating expression of molecules regulating apoptosis and stimulating angiogenesis. In addition, HO-1 contributes in a critical manner to inhibition or termination of inflammation. Consequently, several anticancer strategies aim at targeting HO-1. The inhibition of HO-1 may cause tumour cells to become more sensitive to chemotherapy and radiation therapy. The water-soluble forms of the HO-1 inhibitor Zinc protoporphyrin (ZnPP) have seemed promising in different in-vivo models, in which it has induced growth arrest in tumour cells with few, if any, side effects. Studies have suggested that HO-1 may also function to disrupt the tumour metastasising process, since the expression of the metalloprotease MMP9 is inversely correlated with HO-1 expression. Additionally, HO-1 has anti-inflammatory functions which play a very important role in the negative regulation of the immune system. Immunological targeting of HO-1 might represent an interesting approach, as epitopes derived from HO- 1 have been found exclusively on tumour tissue. Natural HO-1-specific T-cell responses have been identified in cancer patients. Hence, recently HO-1-specific, CD8⁺ regulatory T cells were described in cancer patients, which in concert with HO-1 expression might be responsible for a highly immunosuppressive tumour microenvironment. Here, we summarise current knowledge of the role of HO-1 in cancer, report the different results of the targeting of HO-1 in preclinical and clinical settings, and discuss future opportunities.
authors.forename: Mads Duus
authors.initials: MD
authors.lastname: Hjortsø
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark. mads.christian.hjortsoe@regionh.dk.
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1