RT Journal Article
SR Electronic
T1 Inhibiting Integrin β8 to Differentiate and Radiosensitize Glioblastoma-Initiating Cells
JF Molecular Cancer Research
JO Mol Cancer Res
FD American Association for Cancer Research
SP 384
OP 397
DO 10.1158/1541-7786.MCR-18-0386
VO 17
IS 2
A1 Malric, Laure
A1 Monferran, Sylvie
A1 Delmas, Caroline
A1 Arnauduc, Florent
A1 Dahan, Perrine
A1 Boyrie, Sabrina
A1 Deshors, Pauline
A1 Lubrano, Vincent
A1 Da Mota, Dina Ferreira
A1 Gilhodes, Julia
A1 Filleron, Thomas
A1 Siegfried, Aurore
A1 Evrard, Solène
A1 Kowalski-Chauvel, Aline
A1 Moyal, Elizabeth Cohen-Jonathan
A1 Toulas, Christine
A1 Lemarié, Anthony
YR 2019
UL http://mcr.aacrjournals.org/content/17/2/384.abstract
AB Glioblastomas (GB) are malignant brain tumors with poor prognosis despite treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a subpopulation of GB-initiating cells (GIC), which contribute to tumor aggressiveness, resistance, and recurrence. Some integrins are specifically expressed by GICs and could be actionable targets to improve GB treatment. Here, integrin β8 (ITGB8) was identified as a potential selective target in this highly tumorigenic GIC subpopulation. Using several patient-derived primocultures, it was demonstrated that ITGB8 is overexpressed in GICs compared with their differentiated progeny. Furthermore, ITGB8 is also overexpressed in GB, and its overexpression is correlated with poor prognosis and with the expression of several other classic stem cell markers. Moreover, inhibiting ITGB8 diminished several main GIC characteristics and features, including self-renewal ability, stemness, migration potential, and tumor formation capacity. Blockade of ITGB8 significantly impaired GIC cell viability via apoptosis induction. Finally, the combination of radiotherapy and ITGB8 targeting radiosensitized GICs through postmitotic cell death.Implications: This study identifies ITGB8 as a new selective marker for GICs and as a promising therapeutic target in combination with chemo/radiotherapy for the treatment of highly aggressive brain tumors.