Abstract
Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how β2-microglobulin (β2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. β2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. β2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either β2-M or HFE results in reversion of EMT. These results demonstrate the role of β2-M in cancer metastasis and lethality. Thus, β2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Neoplasms / immunology
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Bone Neoplasms / metabolism*
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Bone Neoplasms / secondary*
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Breast Neoplasms / immunology
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Epithelial-Mesenchymal Transition
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Female
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Gene Knockdown Techniques
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Hemochromatosis Protein
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Humans
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Immunocompromised Host
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Immunohistochemistry
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Iron / metabolism
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Kidney Neoplasms / immunology
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Kidney Neoplasms / metabolism
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Kidney Neoplasms / pathology
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Lung Neoplasms / immunology
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Male
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Mice, Nude
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Neoplasms / immunology
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Neoplasms / metabolism*
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Neoplasms / pathology*
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Transplantation, Heterologous
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beta 2-Microglobulin / antagonists & inhibitors
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beta 2-Microglobulin / biosynthesis
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beta 2-Microglobulin / immunology
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beta 2-Microglobulin / metabolism*
Substances
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HFE protein, human
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Hemochromatosis Protein
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Histocompatibility Antigens Class I
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Membrane Proteins
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beta 2-Microglobulin
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Iron