Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells.

By M. Ho, A. Ng, S. Lam, J. Hung. Cancer Research, 2007

971 citations recorded by the source corpus.

Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the "side population" (SP). In this study, we used flow cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed that SP cells were enriched in tumor-initiating capability compared with non-SP cells. Matrigel invasion assay showed that SP cells also have higher potential for invasiveness. Further characterization of this SP phenotype revealed several stem cell properties. We found evidence for repopulating ability by SP to regenerate a population resembling the original population. SP displayed elevated expression of ABCG2 as well as other ATP-binding cassette transporters and showed resistance to multiple chemotherapeutic drugs. Human telomerase reverse transcriptase expression was higher in the SP, suggesting that this fraction may represent a reservoir with unlimited proliferative potential for generating cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the MCM family of proteins critical to the DNA replication complex, were lower in SP cells, suggesting that a majority of the SP fraction was in the G(0) quiescent state. Sixteen clinical lung cancer samples also displayed a smaller but persistent SP population. These findings indicate that SP is an enriched source of lung tumor-initiating cells with stem cell properties and may be an important target for effective therapy and a useful tool to investigate the tumorigenic process.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a59dcaee8c1c87b43aab8c29b644ddfeac62c5f4

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In Molecular Biology

1. M. Clarke
2. Eric C. Holland
3. C. Harley
4. A. Gurney
5. Jason T. Huse

In Oncology

1. Eric C. Holland
2. M. Clarke

Citations in the corpus

• PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells (2009, background): “Moreover, when isolated from solid tumors, SP cells are more tumorigenic after injection into nude mice (Ho et al., 2007; Patrawala et al., 2005).”
• Telomerase and cancer therapeutics (2008, background): “and some recent studies have suggested that cancer stem or stem-like cells are also telomerase-positiv”
• Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy (2008, background): “. CSC may also enter the cell cycle less frequently, allowing them to resist toxicity by drugs that target highly proliferative cells. Evidence for chemoresistance by stem-like cells in epithelial cell lines and xenogeneic tumor-derived cells has been presented”
• IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. (2007, background): “In regard to the stem cell phenotype of MS, we show here that MS express a variety of genes that are upregulated in normal and cancer stem cell from various tissues, such as Bmi-1 (23, 40), CD44 (28, 29), Oct-4 (27), BCRP-I (33), and CD133 (31, 32).”