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Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer.

Publication ,  Journal Article
Butler, W; Xu, L; Zhou, Y; Cheng, Q; Hauck, JS; He, Y; Marek, R; Hartman, Z; Cheng, L; Yang, Q; Wang, M-E; Chen, M; Zhang, H; Armstrong, AJ; Huang, J
Published in: J Pathol
May 2023

Neuroendocrine (NE) cells comprise ~1% of epithelial cells in benign prostate and prostatic adenocarcinoma (PCa). However, they become enriched in hormonally treated and castration-resistant PCa (CRPC). In addition, close to 20% of hormonally treated tumors recur as small cell NE carcinoma (SCNC), composed entirely of NE cells, which may be the result of clonal expansion or lineage plasticity. Since NE cells do not express androgen receptors (ARs), they are resistant to hormonal therapy and contribute to therapy failure. Here, we describe the identification of glypican-3 (GPC3) as an oncofetal cell surface protein specific to NE cells in prostate cancer. Functional studies revealed that GPC3 is critical to the viability of NE tumor cells and tumors displaying NE differentiation and that it regulates calcium homeostasis and signaling. Since our results demonstrate that GPC3 is specifically expressed by NE cells, patients with confirmed SCNC may qualify for GPC3-targeted therapy which has been developed in the context of liver cancer and displays minimal toxicity due to its tumor-specific expression. © 2023 The Pathological Society of Great Britain and Ireland.

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Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

May 2023

Volume

260

Issue

1

Start / End Page

43 / 55

Location

England

Related Subject Headings

  • Prostatic Neoplasms
  • Pathology
  • Neuroendocrine Cells
  • Neoplasm Recurrence, Local
  • Male
  • Humans
  • Glypicans
  • Biomarkers
  • Adenocarcinoma
  • 3211 Oncology and carcinogenesis
 

Citation

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Butler, W., Xu, L., Zhou, Y., Cheng, Q., Hauck, J. S., He, Y., … Huang, J. (2023). Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer. J Pathol, 260(1), 43–55. https://doi.org/10.1002/path.6063
Butler, William, Lingfan Xu, Yinglu Zhou, Qing Cheng, J Spencer Hauck, Yiping He, Robert Marek, et al. “Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer.J Pathol 260, no. 1 (May 2023): 43–55. https://doi.org/10.1002/path.6063.
Butler W, Xu L, Zhou Y, Cheng Q, Hauck JS, He Y, et al. Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer. J Pathol. 2023 May;260(1):43–55.
Butler, William, et al. “Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer.J Pathol, vol. 260, no. 1, May 2023, pp. 43–55. Pubmed, doi:10.1002/path.6063.
Butler W, Xu L, Zhou Y, Cheng Q, Hauck JS, He Y, Marek R, Hartman Z, Cheng L, Yang Q, Wang M-E, Chen M, Zhang H, Armstrong AJ, Huang J. Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer. J Pathol. 2023 May;260(1):43–55.
Journal cover image

Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

May 2023

Volume

260

Issue

1

Start / End Page

43 / 55

Location

England

Related Subject Headings

  • Prostatic Neoplasms
  • Pathology
  • Neuroendocrine Cells
  • Neoplasm Recurrence, Local
  • Male
  • Humans
  • Glypicans
  • Biomarkers
  • Adenocarcinoma
  • 3211 Oncology and carcinogenesis