Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness

Cristina Richichi, Daniela Osti, Massimiliano Del Bene, Lorenzo Fornasari, Monica Patanè, Bianca Pollo, Francesco Dimeco, Giuliana Pelicci

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) is maintained by a small subpopulation of tumor-initiating cells (TICs). The arduous assessment of TIC frequencies challenges the prognostic role of TICs in predicting the clinical outcome in GBM patients. We estimated the TIC frequency in human GBM injecting intracerebrally in mice dissociated cells without any passage in culture. All GBMs contained rare TICsand were tumorigenic in vivo but only 54% of them grew in vitro as neurospheres. We demonstrated that neurosphere formation in vitro did not foretell tumorigenic ability in vivo and frequencies calculated in vitro overestimated the TIC content. Our findings assert the pathological significance of GBM TICs. TIC number correlated positively with tumor incidence and inversely with survival of tumorbearing mice. Stratification of GBM patients according to TIC content revealed that patients with low TIC frequency experienced a trend towards a longer progression free survival. The expression of either putative stem-cell markers or markers associated with different GBM molecular subtypes did not associate with either TIC content or neurosphere formation underlying the limitations of TIC identification based on the expression of some putative stem cell-markers.

Original languageEnglish
Pages (from-to)71491-71503
Number of pages13
JournalOncotarget
Volume7
Issue number44
DOIs
Publication statusPublished - 2016

Keywords

  • Glioblastoma
  • Limiting dilution assay
  • Neurosphere
  • Tumor-initiating cell frequency
  • Tumorigenicity

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness'. Together they form a unique fingerprint.

Cite this