Side Population in Human Lung Cancer Cell Lines and Tumors Is Enriched with Stem-like Cancer Cells

Abstract

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 tumorinitiating 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. [Cancer Res 2007;67(10):4827-33]

RETRACTED ARTICLE: Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

“…Cancer stem cell (CSC) hypothesis has received more and more attention in recent times for its better explanation of the initiation of relapse and metastasis in several types of carcinomas including gastric carcinoma (Reya et al, 2001;Houghton et al, 2004;McDonald et al, 2008). In recent research, several malignant tumor tissues and cell lines have been discovered to possess CSCs, and include acute lymphoblastic leukemia and several solid tumors like breast, colon, hepatic, prostate, lung, and gastric cancers (Alvi et al, 2003;Chiba et al, 2006;Ho et al, 2007;Ricci-Vitiani et al, 2007;Fukuda et al, 2009;Oates et al, 2009). This has strengthened the hypothesis that the initiation of relapse and metastasis may be caused by CSCs.…”

Progenitor stem cell marker expression by pulmonary carcinomas

“…15 This study was based on immunohistochemistry of archival paraffin-embedded tissue, which limits our ability to include other markers associated with stem cells, such as those used in the detection of antigens by flow cytometry of dissociated tumor cells or cell lines. [30][31][32][33][34] Immunohistochemistry may have also limited our ability to detect antigens that are expressed in a small number of cells. This may be particularly relevant to the low detection of antigen, such as CD133 and CD34.…”

Monitoring microRNAs Using a Molecular Beacon in CD133+/CD338+Human Lung Adenocarcinoma-initiating A549 Cells

“…CD338 (ABCG2), a member of the ATP-binding cassette (ABC) transporter superfamily, is an important determinant of the side population (SP) phenotype (Zhou et al, 2001). SP cells expressing marked by CD338 have stem cell-like capabilities that have found in a variety of solid malignancies and NSCLC (Ho et al, 2007). Furthermore, CD338 can promote resistance to multiple drugs and has been observed in many types of TICs (Bertolini et al, 2009).…”

“…CD133-positive lung CSCs (LCSCs) display a high expression level of ABCG2 (CD338), an ATP-binding cassette (ABC) transporter, which is thought to be responsible for resistance to such chemotherapeutic agents as cisplatin (Zhou et al, 2001;Bertolini et al, 2009). TICs are also present in established lung cancer cell lines, including H460 and A549, which show tumor-initiating capacity in mice and chemotherapeutic drug resistant due to the elevated expression of ABCG2 (Ho et al, 2007).…”