Cancer Research
Research Toward a Cure
Limitless Cell Division and Proliferation
Limitless Cell Division and Proliferation—More examples from the literature:
Most cells can execute only a limited number of cell division cycles. Two barriers are important for this limitation: senescence (a viable but nonproliferative state) and crisis (cell death). To form a macroscopic tumor, cancer cells must circumvent these barriers.
In malignant cells, continued telomere maintenance allows unlimited proliferation. Telomerase is also thought to play a role in cell signaling, apoptosis, and DNA damage repair.
Imetelstat Inhibits Telomerase Activity and Cell Growth in Pediatric Neural Tumors
Figure 1. Telomerase activity is present only in the tumor-initiating cell (TIC) subpopulation of freshly resected gliomas. A) TRAP assay of cells from a freshly resected high-grade glioma (G401) before and after FACS cell sorting, based on CD15 expression. CD15+ cells (13% of cells) show high telomerase activity, but CD15- cells exhibit no activity. C) TRAP assay of adherent (A) and spheroid (S) glioma cell subpopulations extracted from 3 freshly resected high-grade gliomas (G291, G296, G308). The sphere subpopulations from all 3 tumors show a high level of telomerase activity, but adherent cell subpopulations do not. TRAP assay gels were imaged with Odyssey® CLx.
Lack of telomere maintenance is predictive of recurrence in pediatric neural tumors. This study examined telomerase activity, telomere maintenance, and stem cell maturation in tumor subpopulations from freshly resected gliomas. Efficacy of the telomerase inhibitor Imetelstat on neural tumor-initiating cells (TIC) was tested.
- Telomerase activity was assessed with telomeric repeat amplification protocol (TRAP) assays. Cy5 primers were used, and acrylamide gels were imaged with the Odyssey Imager
- Telomerase activity was specific to TIC subpopulations. It was not observed in the majority of tumor cells, or in normal neural stem cells.
- The inhibitor Imetelstat caused loss of self-renewal and growth arrest in a neuroblastoma model, but did not affect normal stem cells.
P Castelo-Branco, C Zhang, T Lipman, M Fujitani, L Hansford, I Clarke, CB Harley, R Tressler, D Malkin, E Walker, DR Kaplan, P Dirks, and U Tabori. Neural tumor-initiating cells have distinct telomere maintenance and can be safely targeted for telomerase inhibition. Clin Cancer Res 17:111-121 (2011).
