Role of cancer stem cells in head-and-neck squamous cell carcinoma – A systematic review

Abstract

Targeting cancer stem cell (CSC) subpopulation within the tumor remains an obstacle for specific therapy in head-and-neck squamous cell carcinoma (HNSCC). Few studies in the literature describe a panel of stem cell makers, however a distinct panel has not been put forth. This systematic review aims to enhance the knowledge of additional markers to accurately relate their expression to tumorigenesis, metastasis, and therapy resistance. Databases, including PubMed, Google Scholar, Ebsco, and Science Direct, were searched from 2010 to 2017 using various combinations of the following keywords: “Stem cell markers in HNSCC” and “chemoresistance and radioresistence in HNSCC.” Original experimental studies (both in vitro and in vivo ) published in English considering stem cell markers in HNSCC, were considered and included. We excluded articles on tumors other than HNSCC, reviews, editorial letters, book chapters, opinions, and abstracts from the analyses. Forty-two articles were included, in which 13 types of stem cell markers were identified. The most commonly expressed CSC markers were CD44, aldehyde dehydrogenase, and CD133, which were responsible for tumorigenesis, self-renewal, and therapy resistance, whereas NANOG, SOX-2, and OCT-4 were involved in metastasis and invasion. Identification of an accurate panel of CSC markers is the need of the hour as nonspecificity of the current markers poses a problem. Further studies with a large sample size would help validate the role of these CSC markers in HNSCC. These CSC proteins can be developed as therapeutic targets for HNSCC therapy, making future treatment modality more specific and effective.

Identification of Muc1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas

“…How that loss of homeostasis from chronic inflammation promotes progression to HNSCC remains largely unknown. The current studies demonstrate that MUC1-C drives STAT1-dependent chronic inflammation in HPV-negative HNSCC cells and thereby induction of the ∆Np63 ( 9, 30–32 ) and SOX2 ( 10, 33 ) TFs that have been linked to HNSCC pathogenesis. We also demonstrate that (i) MUC1-C signaling regulates the NOTCH3 pathway that contributes to the HNSCC CSC state ( 34, 35 ), and (ii) HNSCC cells are dependent on MUC1-C for self-renewal and tumorigenicity.…”

“…SOX2 is essential for self-renewal of basal cells, which are the proposed origin of SCCs ( 30, 59 ). In addition, SOX2 contributes to progression of the SCC CSC state ( 10, 33 ). As found for ∆Np63, targeting MUC1-C in CAL27 and HSC3 cells downregulated SOX2 gene transcription and mRNA levels ( Fig.…”

Combining microfluidic chip and low-attachment culture devices to isolate oral cancer stem cells

“…reported that the three markers CD44, CD133, and ALDH were the most commonly expressed CSC markers in head and neck squamous cell carcinoma. 15 …”

Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation: A Systematic Review

“…(55) The major impediment to HNSCC is the presence of cancer stem cells, which have self-renewal abilities, high proliferation capacity, high migration capacity, drug resistance, resistance to chemo-and radiotherapies, and differentiation capacity. (56) These cells do not have specifi c cell markers known that can be used to identify and specifi cally target these cells, making it diffi cult to completely dry out the HNSCC, prolonging the time of coexistence with the disease. (56) Unlike GBC, HNSCC is easy to identify, however, there is still a long delay for its diagnosis, which ends up being done already in advanced stages, due to the low presentation of symptoms.…”

“…(56) These cells do not have specifi c cell markers known that can be used to identify and specifi cally target these cells, making it diffi cult to completely dry out the HNSCC, prolonging the time of coexistence with the disease. (56) Unlike GBC, HNSCC is easy to identify, however, there is still a long delay for its diagnosis, which ends up being done already in advanced stages, due to the low presentation of symptoms. (57) This delay in diagnosis and the prolongation of the time of living with the HNSCC translates into high expenses with medication and treatments for the various health systems, in addition to an increase in the queues for treatment.…”