Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival

• DOI: 10.1097/cmr.0b013e3283471042
• Publication Date: 2011-05-19T07:51:17Z
• Authors: Maria A. Selim; James L. Burchette; Edith V. Bowers; Gustaaf G. de Ridder; Lihong Mo; Salvatore V. Pizzo; Mario Gonzalez-Gr...
• Keywords: Glucose-regulated protein

A correlation between expression of the glucose-regulated protein 78 kDa (GRP78) in malignant melanoma tumors and poor patient survival is well established. In this study, addition to demonstrating GRP78 tumor tissue, we investigated immune response against a group patients with different progression stages melanoma. Furthermore, analyzed glycosylation status immunoglobulin (Ig) G autoantibodies at these evaluated their capacities affect B-dependent kinase signaling pathway unfolded mechanisms, all known promote cell proliferation survival. We found that disease correlates not only enhanced but also an increase autoantibody serum titers patients. anti-GRP78 IgG changes as progresses. The abnormally glycosylated Fc region asymmetrically Fab region. demonstrate hyperglycosylated IgGs stimulate through pathways. They mimic effects α2-macroglobulin on upregulation X-box binding 1, activating transcription factor 6 α, serine/threonine-protein kinase/endoribonuclease precursor α endoplasmic reticulum stress biomarkers show no effect or activation caspases 3, 9, 12. conclusion, downregulate apoptosis activate which are essential growth