Expansion of CD133-positive glioma cells in recurrent de novo glioblastomas after radiotherapy and chemotherapy

Abstract

Object. Recent evidence suggests that a glioma stem cell subpopulation may determine the biological behavior of tumors, including resistance to therapy. To investigate this hypothesis, the authors examined varying grades of gliomas for stem cell marker expressions and histopathological changes between primary and recurrent tumors.Methods. Tumor samples were collected during surgery from 70 patients with varying grades of gliomas (Grade II in 12 patients, Grade III in 16, and Grade IV in 42) prior to any adjuvant treatment. The samples were subjected to immunohistochemistry for MIB-1, factor VIII, GFAP, and stem cell markers (CD133 and nestin). Histopathological changes were compared between primary and recurrent tumors in 31 patients after radiation treatment and chemotherapy, including high-dose irradiation with additional stereotactic radiosurgery.Results. CD133 expression on glioma cells was confined to de novo glioblastomas but was not observed in lower-grade gliomas. In de novo glioblastomas, the mean percentage of CD133-positive glioma cells in sections obtained at recurrence was 12.2% ± 10.3%, which was significantly higher than that obtained at the primary surgery (1.08% ± 1.78%). CD133 and Ki 67 dual-positive glioma cells were significantly increased in recurrent de novo glioblastomas as compared with those in primary tumors (14.5% ± 6.67% vs 2.16% ± 2.60%, respectively). In contrast, secondary glioblastomas rarely expressed CD133 antigen even after malignant progression following radiotherapy and chemotherapy.Conclusions. The authors' results indicate that CD133-positive glioma stem cells could survive, change to a proliferative cancer stem cell phenotype, and cause recurrence in cases with de novo glioblastomas after radiotherapy and chemotherapy. 1145Abbreviations used in this paper: EBRT = external-beam radiation therapy; GKS = Gamma Knife surgery.

Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T-cell–Engaging Antibody and CD8 T Cells

“…In the latter study, a considerable proportion of tumors contained >10% or even >25% of AC133 þ cells. Furthermore, the frequencies of CD133 þ glioma cells and their proliferation seem to increase considerably at GBM recurrence (41). AC133 þ tumor stem cells could perhaps also be targeted in brain tumors other than GBM.…”

The Role of Astrocytes in Tumor Growth and Progression

“…Interestingly, Singh et al (2003) found CD133 + cells to be tumor initiating, whereas CD133 À cells could not initiate a tumor or self-renew in a mouse xenograft model [118,121]. The levels of CD133 + BTSCs has since been correlated to negative prognoses in gliomas, and have been found to be particularly enriched in recurrent tumors after radiation and chemotherapy [122][123][124]. These findings highlight the importance of stem cells in the overall initiation, malignancy, and recurrence of brain tumors.…”

Targeting cancer stem cells in cancer therapy

“…And CSCs model provides an explanation for the resistance to chemotherapy in some type of tumors [6] . Expression of CD133 in glioblastoma cell population increased after radiation therapy, whether in glioma cell lines or in nude mice [7] . Therefore, strategies that aim to CSCs are of particular interest in cancer therapy [8] .…”