Table 1.

Characteristics of common markers used to describe the cells population with high probability of cancer initiating cells presence in HNSCC.

Marker	Population characteristic	Ref.
CD271	• Only CD271+/CD44+ population contains mostly tumorigenic cells • Loss of CD271 reduces cell proliferation via inhibition of G2-M transition and inhibition of Erk1/2 phosphorylation	103
CD44	• CD44+ cells are more tumorigenic than CD44− • CD44+ cells have primary cellular morphology and express Cytokeratin 5/14 (basal cell marker) • CD44− cells are differentiated squamous epithelial cells and express Involucrin (differentiation cell marker) • CD44+ cells express higher levels of BMI-1 protein than CD44− • There are several CD44 isoforms and only some of them can be used as CICs and radioresistance markers	79, 83
CD133	• CD133+ cells are more invasive, with higher migration and clone-formation ability than CD133− cells; they possess differentiation capacity • CD133+ cells exhibit higher expression of anti-apoptosis genes, higher Bcl-2/Bax ratio and show dysregulated Hedgehog, Wnt signaling pathways and higher Bmi-1 expression • BMI-l seems to be central master of CIC-phenotype in the CD133+ cells through the regulation of p16(INK4A) and p14(ARF) • CD133+ expression is positively associated with more advanced TNM stage, pathological grade and lymph node metastasis • CD133+ patients have shorter overall survival and disease-free survival • CD133 expression negatively correlates with KAI1/CD82 protein and both could be used as independent prognostic factors • CD133+ cells have higher proliferation ratio than CD133− and possess higher expression of Glut-1 important in glucose transport • CD133 gene is over-expressed in SP cells (CD133+ SP) while down-regulation of CD133 reduces number of SP and increases chemosensitivity	104, 105, 106, 107, 108, 109, 110
CD24	• CD24+ cells co-express OCT3/4 and CIP2A proteins • CD24+/CD44+ population is more invasive, more chemoresistant and creates larger tumor compared to CD24-/CD44+ population	97, 111
ALDH	• ALDH+ cells are more tumorigenic than ALDH−; most of ALDH+ cells are CD44+ • ALDH enzyme is probably required for cancer initiating cell activity • Expression of ALDH is observed in CD44+/CD24− cell population; CD44+/CD24-/ALDH+ subpopulation is more aggressive and resistant to therapy than other populations marked by these markers • CD44+/CD24-/ALDH+ subpopulation (as well as only ALDH+ cells) shows up-regulated stemness genes (OCT3/4, Nanog, SOX2, KLF4, BMI-1, Nestin) and the drug-resistant genes (MDR-1, MRP-1, ABCG2); CD44+/CD24-/ALDH1+ population has the most similar gene signature to mesenchymal stem cells (MSC) and MSC-related drift • EMT-related genes are activated in ALDH+ cells and Snail seems to be the most important regulator of CICs phenotype	112, 113
CD166	• CD166+ cells have high capacity of sphere and tumor formation • Patients with high CD166 expression levels have poorer clinical outcome • CD166 expression is associated with tumor recurrence • CD166 enhanced phosphorylation of EGFR and (EGF)/EGFR pathway activation • Stimulation of CD166− cells by EGF causes increased cell tumorigenic ability in vitro and in vivo	114, 115