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

Publication ,  Journal Article
Selim, MA; Burchette, JL; Bowers, EV; de Ridder, GG; Mo, L; Pizzo, SV; Gonzalez-Gronow, M
Published in: Melanoma Res
August 2011

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

Duke Scholars

Published In

Melanoma Res

DOI

EISSN

1473-5636

Publication Date

August 2011

Volume

21

Issue

4

Start / End Page

323 / 334

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Young Adult
  • Unfolded Protein Response
  • Tumor Burden
  • Skin Neoplasms
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Processing, Post-Translational
  • Phosphorylation
  • Oncology & Carcinogenesis
 

Citation

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MLA
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Selim, M. A., Burchette, J. L., Bowers, E. V., de Ridder, G. G., Mo, L., Pizzo, S. V., & Gonzalez-Gronow, M. (2011). Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival. Melanoma Res, 21(4), 323–334. https://doi.org/10.1097/CMR.0b013e3283471042
Selim, Maria A., James L. Burchette, Edith V. Bowers, Gustaaf G. de Ridder, Lihong Mo, Salvatore V. Pizzo, and Mario Gonzalez-Gronow. “Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival.Melanoma Res 21, no. 4 (August 2011): 323–34. https://doi.org/10.1097/CMR.0b013e3283471042.
Selim MA, Burchette JL, Bowers EV, de Ridder GG, Mo L, Pizzo SV, et al. Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival. Melanoma Res. 2011 Aug;21(4):323–34.
Selim, Maria A., et al. “Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival.Melanoma Res, vol. 21, no. 4, Aug. 2011, pp. 323–34. Pubmed, doi:10.1097/CMR.0b013e3283471042.
Selim MA, Burchette JL, Bowers EV, de Ridder GG, Mo L, Pizzo SV, Gonzalez-Gronow M. Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival. Melanoma Res. 2011 Aug;21(4):323–334.

Published In

Melanoma Res

DOI

EISSN

1473-5636

Publication Date

August 2011

Volume

21

Issue

4

Start / End Page

323 / 334

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Young Adult
  • Unfolded Protein Response
  • Tumor Burden
  • Skin Neoplasms
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Processing, Post-Translational
  • Phosphorylation
  • Oncology & Carcinogenesis