Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line

TLDR

Both stem cells and cancer cells are thought to be capable of unlimited proliferation, yet some cancers appear to contain stem‑like cells. The study aimed to determine whether long‑term cultured malignant cell lines harbor a minor stem‑cell subpopulation, specifically a side population (SP), that can be maintained indefinitely and is essential for malignancy. The authors maintained C6 glioma SP cells in serum‑free medium supplemented with basic fibroblast growth factor and platelet‑derived growth factor. The study found that a small side‑population of C6 glioma cells, enriched in stem‑like properties, can self‑renew, generate both SP and non‑SP cells, drive in vivo malignancy, and differentiate into neurons and glial cells, indicating that such SP cells are essential for cancer cell line malignancy.

Abstract

Both stem cells and cancer cells are thought to be capable of unlimited proliferation. Paradoxically, however, some cancers seem to contain stem-like cells (cancer stem cells). To help resolve this paradox, we investigated whether established malignant cell lines, which have been maintained for years in culture, contain a subpopulation of stem cells. In this article, we show that many cancer cell lines contain a small side population (SP), which, in many normal tissues, is thought to contain the stem cells of the tissue. We demonstrate that in the absence of serum the combination of basic fibroblast growth factor and platelet-derived growth factor maintains SP cells in the C6 glioma cell line. Moreover, we show that C6 SP cells, but not non-SP cells, can generate both SP and non-SP cells in culture and are largely responsible for the in vivo malignancy of this cell line. Finally, we provide evidence that C6 SP cells can produce both neurons and glial cells in vitro and in vivo . We propose that many cancer cell lines contain a minor subpopulation of stem cells that is enriched in an SP, can be maintained indefinitely in culture, and is crucial for their malignancy.