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Updated: Mar 24, 2026

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
06:32

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells

Published on: September 1, 2010

16.9K

PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma

Alok R Singh1, Shweta Joshi1, Muamera Zulcic1

  • 1Department of Pediatrics, Moores Cancer Center, UC San Diego Health System, La Jolla, CA, United States of America.

Plos One
|March 4, 2016
PubMed

Insights

Sonic hedgehog medulloblastoma is driven by CD15+ tumor propagating cells. Targeting phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) with inhibitors shows promise, while chemotherapy is ineffective against these cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Sonic hedgehog (SHH) medulloblastoma (MB) is driven by CD15+ tumor propagating cells (TPCs), also known as cancer stem cells (CSCs).
  • The precise biology and therapeutic vulnerabilities of these CD15+ TPCs remain largely unknown.
  • Understanding the role of signaling pathways like PTEN/PI-3K is critical for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) signaling in CD15+ TPCs driving SHH medulloblastoma.
  • To evaluate the efficacy of PI-3K inhibitors and conventional chemotherapy agents against these TPCs.
  • To establish the genomic similarity between the mouse model and human SHH MB subgroup.

Main Methods:

  • Utilized the ND2-SmoA1 transgenic mouse model for MB.
  • Employed mouse genetics and patient-derived xenografts (PDXs).
  • Assessed sensitivity of CD15+ TPCs to pan PI-3K inhibitors, chemotherapy (cisplatin, temozolomide), and SHH inhibitor (NVP-LDE-225) in vitro and in vivo.

Main Results:

  • CD15+ TPCs are essential for SmoA1Tg-driven tumorigenicity and are regulated by PTEN and PI-3K signaling.
  • CD15+ TPCs are selectively sensitive to pan PI-3K inhibitors but resistant to current chemotherapy and SHH inhibitors.
  • Genomic analysis showed similarity between the SmoA1Tg mouse model and human SHH MB subgroup.

Conclusions:

  • PTEN plays a significant role in MB TPC signaling and biology.
  • PI-3K inhibitors effectively target and suppress CD15+ cancer stem cells in both mouse and human MB.
  • Pan PI-3K inhibitors represent a promising therapeutic strategy for SHH medulloblastoma, potentially enhanced by combination with chemotherapy.

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