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Updated: Jun 24, 2025

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
07:16

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

Published on: March 14, 2014

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GD2 and its biosynthetic enzyme GD3 synthase promote tumorigenesis in prostate cancer by regulating cancer stem cell

Aaqib M Bhat1,2, Bhopal C Mohapatra3,4, Haitao Luan1

  • 1Eppley Institute for Research in Cancer and Allied Diseases, 985805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.

Scientific Reports
|June 12, 2024
PubMed

Insights

Di-ganglioside GD2 is found in prostate cancer (PC) cells, especially in metastatic tumors. Targeting GD2 may offer new therapeutic options for advanced PC by impacting cancer stem cells.

Area of Science:

  • Oncology
  • Cancer Biology
  • Biochemistry

Background:

  • Advanced prostate cancer (PC) remains a significant cause of cancer mortality despite improved loco-regional management.
  • Novel therapeutic targets are needed to address tumor progression in advanced PC.
  • The role of di-ganglioside GD2, an FDA-approved target in neuroblastoma, is unexplored in PC.

Purpose of the Study:

  • To investigate the expression and functional role of GD2 in prostate cancer.
  • To determine if GD2 is associated with aggressive PC phenotypes, including castration-resistant PC (CRPC) and cancer stem cells.
  • To evaluate the therapeutic potential of targeting GD2 or its biosynthetic pathway in PC.

Main Methods:

  • Analysis of GD2 expression in PC patient samples and cell lines.
  • Upregulation of GD2 expression by inducing lineage progression and enzalutamide resistance in CRPC models.
  • Assessment of GD2 expression in tumorsphere formation assays to evaluate cancer stem cell enrichment.
  • CRISPR-Cas9 knockout of GD3 Synthase (GD3S), the rate-limiting enzyme in GD2 biosynthesis, in GD2-high CRPC cells.
  • Evaluation of in vitro oncogenic traits and in vivo tumor growth in bone-implanted xenograft models.

Main Results:

  • GD2 is expressed in a subset of PC cells, with higher prevalence in metastatic tumors.
  • GD2 expression is upregulated in PC cell lines upon induction of lineage progression or enzalutamide resistance.
  • GD2-high cell fraction is enriched in tumorsphere-forming cells, indicating association with cancer stem cell properties.
  • GD3S knockout in CRPC cells significantly impaired in vitro oncogenic traits and in vivo tumor growth.
  • GD3S knockout reduced cancer stem cell and epithelial-mesenchymal transition marker expression.

Conclusions:

  • GD2 expression is linked to aggressive features of prostate cancer, including stemness and resistance.
  • GD3S and its product GD2 play a role in PC tumorigenesis by maintaining cancer stem cells.
  • GD2 represents a potential therapeutic target for advanced prostate cancer.
Keywords:
Cancer stem cellsCastration-resistant prostate cancerGD2GD3 synthaseMetastasisProstate cancer

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