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Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma.

Publication ,  Journal Article
de Ridder, GG; Gonzalez-Gronow, M; Ray, R; Pizzo, SV
Published in: Melanoma Res
February 2011

Autoantibodies that react with GRP78 expressed on the cell-surface of many tumor cell lines occur in the sera of patients with prostate cancer, melanoma, and ovarian cancer. These autoantibodies are a negative prognostic factor in prostate cancer and, when purified, stimulate tumor cell proliferation in vitro. It is unclear, however, whether these immunoglobulin Gs are merely a biomarker, or whether they actually promote the tumor growth in vivo. We immunized C57Bl/6 mice with recombinant GRP78 and then implanted the B16F1 murine melanoma cell line as flank tumors. We used the antisera from these mice for in-vitro cell signaling and proliferation assays. The immunodominant epitope in patients with cancer was well represented in the antibody repertoire of these immunized mice. We observed significantly accelerated tumor growth, and shortened survival in GRP78-immunized mice compared with controls. Furthermore, antisera from these mice, and purified anti-GRP78 immunoglobulin G from similarly immunized mice, stimulate Akt phosphorylation and proliferation in B16F1 and human DM6 melanoma cells in culture. These studies show a causal link between a humoral response to GRP78 and the progression of cancer in a murine melanoma model. They support the hypothesis that such autoantibodies are involved in the progression of human cancers and are not simply a biomarker. As GRP78 is present on the surface of many types of cancer cells, this hypothesis has broad clinical and therapeutic implications.

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Published In

Melanoma Res

DOI

EISSN

1473-5636

Publication Date

February 2011

Volume

21

Issue

1

Start / End Page

35 / 43

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Skin Neoplasms
  • Recombinant Proteins
  • Phosphorylation
  • Peptides
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Melanoma
  • Humans
 

Citation

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de Ridder, G. G., Gonzalez-Gronow, M., Ray, R., & Pizzo, S. V. (2011). Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma. Melanoma Res, 21(1), 35–43. https://doi.org/10.1097/CMR.0b013e3283426805
Ridder, Gustaaf G. de, Mario Gonzalez-Gronow, Rupa Ray, and Salvatore V. Pizzo. “Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma.Melanoma Res 21, no. 1 (February 2011): 35–43. https://doi.org/10.1097/CMR.0b013e3283426805.
de Ridder GG, Gonzalez-Gronow M, Ray R, Pizzo SV. Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma. Melanoma Res. 2011 Feb;21(1):35–43.
de Ridder, Gustaaf G., et al. “Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma.Melanoma Res, vol. 21, no. 1, Feb. 2011, pp. 35–43. Pubmed, doi:10.1097/CMR.0b013e3283426805.
de Ridder GG, Gonzalez-Gronow M, Ray R, Pizzo SV. Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma. Melanoma Res. 2011 Feb;21(1):35–43.

Published In

Melanoma Res

DOI

EISSN

1473-5636

Publication Date

February 2011

Volume

21

Issue

1

Start / End Page

35 / 43

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Skin Neoplasms
  • Recombinant Proteins
  • Phosphorylation
  • Peptides
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Melanoma
  • Humans