Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma

Jing Han,Raj K Puri,Syed R Husain,Toshio Fujisawa

doi:10.1186/1471-2407-14-173

Abstract

BackgroundCurrent evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC.MethodsCD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo.ResultsOur results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population.ConclusionOur study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy.

Highlights

Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC)
We found that a small population of CD24+/CD44+ cells existed in head and neck squamous cell carcinoma (HNSCC) [21]
Isolation and characterization of CD24+/CD44+ cells in HNSCC cell lines To determine the percentage of the putative cancer stemlike cells in the HNSCC cell population, cell suspensions from cell lines A253 and KCCT873 were analyzed and sorted for cell surface markers CD24 and CD44 by flow cytometry

Summary

Introduction

Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). Squamous cell carcinoma of head and neck (HNSCC) is a heterogeneous disease [1]. HNSCC frequently shows local recurrence and metastasis after the initial treatment of the primary tumor [3]. Mortality from this disease remains high because of the development of metastases and therapy-resistant local and regional. Recent evidence suggests that small populations of tumor-initiating cells or cancer stem cells (CSC) are responsible for initiation, tumorigenesis, progression, and metastasis [4]. If CSCs can be identified prospectively and isolated, we should be able to identify new diagnostic markers and potential therapeutic targets

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Conclusion