| Background |
Glycoprotein non-metastatic gene B (GPNMB) is a type I transmembrane glycoprotein overexpressed in many types of cancer. The GPNMB glycoprotein is involved in many physiological processes, including mediating transport of late melanosomes to keratinocytes regulating osteoblast and osteoclast differentiation and function stimulating dendritic cell maturation, promoting adhesion of dendritic cells to endothelial cells enhancing autophagosome fusion to lysosomes in tissue repair, and regulating degradation of cellular debrisWhile typical GPNMB expression is seen in tissues including skin, heart, kidney, lung, liver, and skeletal muscle research studies show elevated GPNMB expression often contributes to the metastatic phenotype in numerous cancers. GPNMB is typically localized to intracellular compartments in normal cells but investigators found it primarily on the cell surface of tumor cells. Differential localization and expression, and the role of GPNMB as a tumor promoter in many cancer types make this protein a viable therapeutic target.The GPNMB ectodomain can be cleaved by matrix metalloproteinases and shed from the cell surface. Research studies identify the sheddase ADAM10 as one peptidase responsible for cleavage of the GPNMB ectodomain at the surface of breast cancer cells. Shedded GPNMB ectodomains may promote angiogenesis by inducing endothelial cell migration.
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