Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and the response to TRAIL-induced apoptosis

Ling Qi, Anita Bellail, Michael R. Rossi, Zhaobin Zhang, Hui Pang, Stephen Hunter, Cynthia Cohen, Carlos S. Moreno, Jeffrey J. Olson, Shibo Li, Chunhai Hao

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recent studies suggest that cancer stem cells (CSCs) are responsible for cancer resistance to therapies. We therefore investigated how glioblastoma-derived CSCs respond to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Neurospheres were generated from glioblastomas, characterized for CSC properties including self-renewal, cell differentiation and xenograft formation capacity, and analyzed for TRAIL-induced apoptosis, CASP8 genomic status, and caspase-8 protein expression. The neurosphere NSC326 was sensitive to TRAIL-induced apoptosis as evidenced by cell death and caspase-8, -3, and -7 enzymatic activities. In contrast, however, the neurosphere NSC189 was TRAIL-resistant. G-banding analysis identified five chromosomally distinguishable cell populations in the neurospheres. Fluorescence in situ hybridization revealed the variation of chromosome 2 copy number in these populations and the loss of CASP8 locus in 2q33-34 region in a small set of cell populations in the neurosphere. Immunohistochemistry of NSC189 cell blocks revealed the lack of caspase-8 protein in a subset of neurosphere cells. Western blotting and immunohistochemistry of human glioblastoma tumors demonstrated the expression of caspase-8 protein in the vast majority of the tumors as compared to normal human brain tissues that lack the caspase-8 expression. This study shows heterogeneity of glioblastomas and derived CSCs in the genomic status of CASP8, expression of caspase-8, and thus responsiveness to TRAIL-induced apoptosis. Clinic trials may consider genomic analysis of the cancer tissue to identify the genomic loss of CASP8 and use it as a genomic marker to predict the resistance of glioblastomas to TRAIL apoptosis pathway-targeted therapies.

Original languageEnglish (US)
Pages (from-to)1150-1164
Number of pages15
JournalApoptosis
Volume16
Issue number11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Caspase 8
Glioblastoma
Neoplastic Stem Cells
Apoptosis
Stem cells
Tumors
Neoplasms
Immunohistochemistry
Cells
Tissue
Population
Proteins
Chromosomes, Human, Pair 2
Cell death
Chromosomes
Fluorescence In Situ Hybridization
Heterografts
Caspase 3
Cell Differentiation
Brain

Keywords

  • Apoptosis
  • Cancer stem cells
  • Caspase-8
  • Glioblastoma
  • TRAIL

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and the response to TRAIL-induced apoptosis. / Qi, Ling; Bellail, Anita; Rossi, Michael R.; Zhang, Zhaobin; Pang, Hui; Hunter, Stephen; Cohen, Cynthia; Moreno, Carlos S.; Olson, Jeffrey J.; Li, Shibo; Hao, Chunhai.

In: Apoptosis, Vol. 16, No. 11, 01.11.2011, p. 1150-1164.

Research output: Contribution to journalArticle

Qi, L, Bellail, A, Rossi, MR, Zhang, Z, Pang, H, Hunter, S, Cohen, C, Moreno, CS, Olson, JJ, Li, S & Hao, C 2011, 'Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and the response to TRAIL-induced apoptosis', Apoptosis, vol. 16, no. 11, pp. 1150-1164. https://doi.org/10.1007/s10495-011-0645-6
Qi, Ling ; Bellail, Anita ; Rossi, Michael R. ; Zhang, Zhaobin ; Pang, Hui ; Hunter, Stephen ; Cohen, Cynthia ; Moreno, Carlos S. ; Olson, Jeffrey J. ; Li, Shibo ; Hao, Chunhai. / Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and the response to TRAIL-induced apoptosis. In: Apoptosis. 2011 ; Vol. 16, No. 11. pp. 1150-1164.
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