A distinct “side population” of cells with high drug efflux capacity in human tumor cells

TLDR

Side‑population stem cells, known for high drug‑efflux capacity, have been identified in various mammalian tissues. This study aimed to determine whether analogous side‑population cells exist in human tumors. Researchers examined primary neuroblastoma cells from 23 patients and multiple tumor cell lines to identify such populations. A distinct side population was present in 65 % of neuroblastoma samples, expanded ex vivo, displayed asymmetric division, expressed ABCG2/ABCA3, and efficiently expelled cytotoxic drugs, and similar cells were also found in breast, lung, and glioblastoma lines, indicating a chemoresistant cancer‑stem‑cell phenotype.

Abstract

A subset of stem cells, termed the “side population” (SP), has been identified in several tissues in mammalian species. These cells maintain a high efflux capability for antimitotic drugs. We have investigated whether functionally equivalent stem cells also may be detected in human cancers. We initially examined primary tumor cells from 23 patients with neuroblastoma and cell lines derived from a range of other tumors. A distinct SP was found in neuroblastoma cells from 15 of 23 patients (65%). The SP was capable of sustained expansion ex vivo and showed evidence for asymmetric division, generating both SP and non-SP progeny. These cells also expressed high levels of ABCG2 and ABCA3 transporter genes and had a greater capacity to expel cytotoxic drugs, such as mitoxantrone, resulting in better survival. A SP also was detected in breast cancer, lung cancer, and glioblastoma cell lines, suggesting that this phenotype defines a class of cancer stem cells with inherently high resistance to chemotherapeutic agents that should be targeted during the treatment of malignant disease.