β2-Microglobulin-mediated Signaling as a Target for Cancer Therapy

Title:β2-Microglobulin-mediated Signaling as a Target for Cancer Therapy

Volume: 14 Issue: 3

Author(s): Takeo Nomura, Wen-Chin Huang, Haiyen E. Zhau, Sajni Josson, Hiromitsu Mimata and Leland W. K. Chung

Affiliation:

Keywords: Anti-β2-m antibody, apoptosis, β2-microglobulin (β2-m), osteomimicry.

Abstract: β2-microglobulin (β2-m) has become the focus of intense scrutiny since the discovery of its undesirable roles promoting osteomimicry and cancer progression. β2-m is a well-known housekeeping protein that forms complexes with the heavy chain of major histocompatibility complex class I molecules, which are heterodimeric cell surface proteins that present antigenic peptides to cytotoxic T cells. On recognition of foreign peptide antigens on cell surfaces, T cells actively bind and lyse antigen-presenting cancer cells. In addition to its roles in tumor immunity, β2-m has two different functions in cancer cells, either tumor promoting or tumor suppressing, in cancer cell context-dependent manner. Our studies have demonstrated that β2-m is involved extensively in the functional regulation of growth, survival, apoptosis, and even metastasis of cancer cells. We found that β2-m is a soluble growth factor and a pleiotropic signaling molecule which interacts with its receptor, hemochromatosis protein, to modulate epithelial-to-mesenchymal transition (EMT) through iron-responsive pathways. Specific antibodies against β2-m have remarkable tumoricidal activity in cancer, through β2-m action on iron flux, alterations of intracellular reactive oxygen species, DNA damage and repair enzyme activities, β-catenin activation and cadherin switching, and tumor responsiveness to hypoxia. These novel functions of β2-m and β2-m signaling may be common to several solid tumors including human lung, breast, renal, and prostate cancers. Our experimental results could lead to the development of a novel class of antibody-based pharmaceutical agents for cancer growth control. In this review, we briefly summarize the recent data regarding β2-m as a promising new cancer therapeutic target and discuss antagonizing this therapeutic target with antibody therapy for the treatment of localized and disseminated cancers.

Cite this article as:

Nomura Takeo, Huang Wen-Chin, Zhau E. Haiyen, Josson Sajni, Mimata Hiromitsu and Chung W. K. Leland, β2-Microglobulin-mediated Signaling as a Target for Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (3) . https://dx.doi.org/10.2174/18715206113139990092