Article

Head and Neck Cancer Stem Cells: The Side Population

The Laryngoscope (Impact Factor: 2.03). 03/2011; 121(3):527 - 533. DOI: 10.1002/lary.21032

ABSTRACT The cancer stem cell (CSC) theory concludes that a subpopulation of cancer cells, the cancer stem cells, can self-renew and are responsible for tumor growth. Previous studies have identified cells able to efflux Hoechst 33342 dye as the side population (SP). SP cells and CSCs share many characteristics, suggesting the SP isolated from malignant tumors contains CSCs.
Experimental Study.
The SP was isolated from a head and neck cancer cell line and analyzed for CSC-like characteristics.
The SP demonstrated the ability to reproduce both SP and non-side population (NSP) cells from as few as one cell. The SP had lower expression of active β-catenin and more resistance to 5-fluorouracil; the SP also demonstrated greater expression of Bmi-1 (4.3-fold) and ABCG2 (1.4-fold). SP cells were able to produce tumors in an animal model, whereas NSP were not. SPs were identified in two primary human tumors.
This work adds to the evidence that the SP in head and neck cancer represents cells with CSC properties and provides a method by which CSCs can be isolated and studied. Laryngoscope, 2011

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    • "Conversely, we found CK2 inhibition reciprocally induced TAp73-inducible growth arrest and proapoptotic genes CDKN2A(p21) and PUMA in HNSCC [16; Suppl Figure 1], indicating a pivotal role as a switch regulating genes that determine cell fate. Concordantly, CK2 inhibition attenuated the SP subset, clonogenicity, and sphere formation, linked to CSC phenotype and tumorgenicity in HNSCC and other cancers [6]. We found that CK2 inhibition enhanced TAp73 expression and dependent repression of several known CSC transcription factor genes in two independent lines from an HNSCC subset overexpressing TAp73 with mtTP53. "
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    • "Cancer stem-like side population (SP) cells have been successfully identified in a wide range of solid tumors, including breast cancer [1], [2], hepatocellular carcinoma [3]–[7], lung cancer [8], [9], gastrointestinal cancer [10]–[12], prostate cancer [13], gallbladder cancer [14], ovarian cancer [15], endometrial cancer [16], pancreatic cancer [17], [18], urological cancer [19], [20], glioblastoma [21], melanoma [22], osteosarcoma [23], [24], mesenchymal neoplasms [25], nasopharyngeal cancer [26], oral cancer [27], [28], and other head and neck cancers [29], [30]. However, most of these investigations have been performed using established cancer cell lines. "
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    • "They are involved in resistance to chemotherapy because of their ability to efflux the drug from the cell and prevent the action of the chemotherapeutic agent.58 Cells of head and neck carcinoma were isolated using this method and exhibited increased clonogenicity and tumorigenicity in xenotransplantation.59–60 "
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