β2-Microglobulin Induces Epithelial to Mesenchymal Transition and Confers Cancer Lethality and Bone Metastasis in Human Cancer Cells

Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how beta 2-microglobulin (beta 2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. beta 2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. beta 2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either beta 2-M or HFE results in reversion of EMT. These results demonstrate the role of beta 2-M in cancer metastasis and lethality. Thus, beta 2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy. Cancer Res; 71(7); 2600-10. (C)2011 AACR.