2-microglobulin ( 2 m ) , a structurally light chain of major histocompatibility complex ( mhc ) class i molecules , is expressed on the surface of all nucleated cells . 2 m non - covalently interacts with the heavy chain of mhc class i to function in the presentation of antigenic peptide fragment to cytotoxic ( cd8 + ) t lymphocytes . in the absence of 2 m , most mhc class i molecules become less expressed on the surface of cells . transfection of 2m - deficiency cells with er - retained 2 m restored the function of mhc class i , supporting a role of 2 m as chaperone for mhc folding . nevertheless , 2 m is present as a soluble form at low levels in different bodily fluids under physiological conditions . it is increasingly recovered in patients with chronic kidney disease and certain malignancies , including liquid and solid tumors . the elevated level of 2 m in body fluid is significantly associated with tumor status and poor prognosis . it is believed that cancer cells frequently downregulate the expression of mhc class i to avoid immune surveillance , allowing gain - of - function via the secretion of free 2 m . thus , the free 2 m is widely implicated in association with mhc class i - loss tumors . there is convincing evidence that 2 m acts as a growth - promoting factor and signal molecule in a variety of cancer cells [ 68 ] . overexpression of 2 m facilitates the invasion and migration of cancer cells of different origin , supporting the increased levels of 2 m positively correlated with advanced - stage tumors . 2 m gain - of - function is achieved by regulating the androgen receptor and a cyclic amp - dependent protein kinase a signaling pathway in prostate cancer . a panel of genes related to cell growth , survival , signaling , and angiogenesis is therefore expressed to trigger tumor progression and cause bone metastasis . similar results were found in human cancer renal cells , showing that 2 m promotes tumor growth via the activation of vascular endothelial growth factor axis . apart from the finding of 2 m as an important prognostic and survival factor in a range of malignancies , it also becomes an attractive therapeutic target . monoclonal antibodies ( mabs ) against 2 m have a surprising apoptotic effect on prostate cancer , renal cell carcinoma ( rcc ) , myeloma , and other hematological malignancies [ 912 ] . yang et al .   demonstrated that mabs induce apoptosis in myeloma cells by recruiting mhc class i molecules to lipid rafts and by excluding growth factor receptors . similarly , huang et al .   revealed that 2m - specific mab decreases lipid levels in prostate cancer cells to make a link between 2m - mediated intracellular signaling axis and lipid rafts in the cell membrane . this may explain why 2 m mabs - induced apoptosis in cancers is mediated via quite similar signaling pathways  the inhibition of pi3k / akt , mapk , and bcl-2 , and the activation of caspases - dependent cascade  supporting the role of 2 m as a mitogenic factor . of note , 2m - specific mabs have a higher affinity for surface - bound rather than the soluble 2 m and display differential sensitivity to malignant cells but not to normal cells , suggesting that the integrity of lipid rafts is an important factor for both apoptotic and survival signaling . strikingly , cao et al .   reported the effectiveness of igm anti-2 m mabs exhibiting more potent activity than igg mabs at inducing tumor cells apoptosis in vitro and in vivo . the enhanced activity of igm mabs in tumor cell apoptosis mainly relies on the pentameric structure of the igm . apparently , these studies support that 2m - specific mab is a promising therapeutic agent for the treatment of several types of malignancies , although further work is needed to evaluate the potential cytotoxicity of the antibody targeting approach . based on a broad range of evidence , it is believed that 2 m acts as a hormone - like molecule to trigger pleiotropic signaling via a ligand - to - receptor binding mechanism . until recently , a noteworthy aspect to 2 m in cancer cell signaling was to identify hemochromatosis ( hfe ) protein with which 2 m induces epithelial - mesenchymal transition ( emt ) and confers cancer lethality and bone metastasis in a variety of human cancer cells . on the contrary , inhibition of 2 m this suggests that 2 m binds with hfe protein , namely 2 m receptor , in association with transferring receptor to modulate iron homeostasis and activate iron - responsive hif-1 ( hypoxia inducible factor-1 ) signaling in cancer cells . because the hif signaling cascade is activated by the effects of hypoxia , which keeps cells from differentiating , 2m - derived upregulation of hif-1 mediates emt and eventually promotes metastasis for cancer progression . previously , chen et al .   revealed that overexpression of 2 m is associated with poor survival in patients with oral cavity squamous cell carcinoma ( ocscc ) and contributes to oral cancer cell migration and invasion . the expression level of 2 m in the cytoplasm and cytoplasm membrane of ocscc epithelial cells at various stages was compared with that in normal oral mucosa , clearly showing that 2 m localizes largely in the cytoplasm of tumor samples ( ~9092% in a total of 256 cases ) rather than in the plasma membrane . this suggests that the increased accumulation of 2 m in the cytoplasm of ocscc is significantly correlated with a relatively advanced tumor stage . this highlights the dramatic changes in 2 m localization from cytoplasm membrane to cytoplasm between normal and tumor stages of ocscc . this feature was also reported by nomura et al . , who found that 2 m expression , in a few cases , localized in the cytoplasm of human rcc . thus , intracellular accumulation of 2 m must play a pivotal role in cancer cell signaling and may present a potential target for therapy . cancerous cells in 2 m loss - of - function are thought to avoid immune surveillance . although 2m - mediated key molecular events such as tumor growth , cancer cells invasion , and metastasis can be attenuated by 2m - specific mabs , questions about translocation of 2 m from plasma membrane to cytoplasm in advanced - stage tumors
2-microglobulin ( 2 m ) functions as a chaperon to maintain structural stability of mhc class i complex that is associated with antigen presentation to cytotoxic ( cd8 + ) t lymphocytes . 
 cancerous cells in 2 m loss - of - function are thought to avoid immune surveillance . as increased level of 2 m present in tissue / serum 
 is significantly associated with tumor status in various cancers , 2 m may become an important prognostic and survival factor in a range of malignancies . 
 it is believed that 2 m acts as hormone - like molecule to trigger a pleiotropic signaling via a ligand - to - receptor binding mechanism . 
 anti-2 m monoclonal antibodies successfully induce apoptosis in malignant cells , suggesting a surprising therapeutic approach . of note 
 , 2 m is largely localized in the cytoplasm of advanced oral cavity squamous cell carcinoma ( ocscc ) , in contrast to that in the plasma membrane of normal oral mucosa . 
 this suggests that 2m - derived intracellular signaling might be preceded by its accumulation in the cytoplasm of epithelial cells of tumors . 
 hence , translocation of 2 m from cell surface to cytoplasm in advanced tumors may shed light on the mechanism of 2m - mediated tumorigenesis .