Glycoprotein Nmb (GPNMB), also known as osteoactivin, is a type I transmembrane glycoprotein. It is involved in various cellular functions, including cell migration, proliferation, invasion, adhesion, and differentiation . GPNMB is expressed in a variety of cell types, including melanocytes, osteoclasts, osteoblasts, and dendritic cells . It is also overexpressed in various cancer types .
GPNMB is a human fragment protein expressed in HEK 293 cells. The recombinant form of GPNMB typically includes a His tag at the C-terminus for purification purposes . The protein is expressed in the 22 to 486 amino acid range, with a purity greater than 95% and an endotoxin level of less than 1 EU/µg . The molecular mass of the recombinant protein is approximately 55.8 kDa, but it migrates at approximately 70-115 kDa in SDS-PAGE due to glycosylation .
GPNMB plays a crucial role in bone development by regulating the differentiation and activities of both osteoblasts and osteoclasts . It is also involved in the pathogenesis of autoimmune diseases, neurodegenerative diseases, and various malignancies . In the context of tumor biology, GPNMB binds to α5β1 fibronectin receptors, promoting tumor invasion and metastasis .
GPNMB can be stimulated by various cytokines and growth factors, including granulocyte-macrophage colony-stimulating factors, transforming growth factor-β, interleukin-10, and interferon-γ . The release of a soluble GPNMB fragment, cleaved by the metalloproteinase ADAM10, initiates a cascade of interactions with various molecular partners, including tyrosine kinase receptors, integrins, and heparan sulfate proteoglycans . These interactions play a significant role in adaptive immunity and inflammation regulation .
GPNMB is expressed in certain cancers, including melanoma, glioma, and breast cancer cells . Its expression in macrophages negatively regulates inflammation, making it a potential therapeutic target for inflammatory diseases . The protein’s role in promoting tumor invasion and metastasis also makes it a target for cancer therapy .