Characterisation of a subpopulation of CD133+ cancer stem cells from Chinese patients with oral squamous cell carcinoma

Abstract

Cancer stem cells (CSCs) play a critical role in cancer development and growth. The aim of this study was to identify and isolate cScs from populations of primary oral squamous cell carcinoma (OSCC) cells, which were obtained from OSCC specimens and identified by cell morphology and immunohistochemical staining for keratin. CD133 + cells detected by flow cytometry comprised 0.41 ± 0.06% of primary OSCC cells and were isolated from primary OSCC cell populations using magnetic-activated cell sorting, revealing that 93.39% of high-purity CD133 + cells were in the G0/ G1 phase of the cell cycle. Additionally, the growth rate of CD133 + cells was higher than that of CD133 − cells, and in vivo tumourigenesis experiments showed that the tumourigenic ability of CD133 + cells was markedly stronger than that of CD133 − cells. Moreover, CD133 + cells showed increased chemotherapeutic resistance to cisplatin and higher self-renewal ability according to sphere-formation assay, as well as higher mRNA levels of stemness-associated genes, including NANOG, SOX2, ALDH1A1, and OCT4. These results indicated that OSCC cells, which share certain characteristics of CSCs, harbour CD133 + cells potentially responsible for OSCC aggressiveness, suggesting CD133 as a potential prognostic marker and therapeutic target. Head and neck cancer (HNC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) the most common type of HNC and accounting for >90% of all oral cancers 1,2. Smoking, drinking, and chewing areca nuts are considered risk factors for OSCC, which can affect any part of the mouth, including the lips, tongue, and throat 3. Furthermore, when patients develop OSCC, they experience maxillofacial deformity and psychological trauma in addition to common symptoms of cancer. Although there have been advances in surgical techniques and chemotherapeutic strategies for OSCC, the patient survival rate remains low 4. Cisplatin is the first-line chemotherapeutic drug currently used to treat patients with locally advanced, resectable OSCC; however, cisplatin resistance poses a major challenge for its clinical application 5 and is considered the critical cause of tumour recurrence in OSCC patients 6. Therefore, a better understanding of the mechanisms underlying OSCC recurrence is required to develop novel therapeutic strategies 7. Studies have increasingly focused on the roles of cancer stem cells (CSCs) in cancer invasion and recurrence 8. CSCs represent highly heterogeneous subpopulations with functional heterogeneity in their respective tumours and are characterised by infinite proliferation, self-renewal, chemotherapeutic resistance, and multidirectionality 9. The role of CSCs was previously demonstrated in the development and therapeutic resistance of liver cancer 10. Similar to their roles in other malignancies, CSCs also play a pivotal role in OSCC development and progression 11,12. The study of CSCs, also referred to as tumour-initiating cells 13 , has recently become among the most popular research dire...

Eldecalcitol inhibits the progression of oral cancer by suppressing the expression of GPx‐1

“…It has a high rate of regional lymphatic metastasis and poor apy drugs, such as cisplatin, have many side effects. Moreover, the chemotherapeutic resistance of tumor cells to cisplatin is increasing (Ma et al, 2020). Therefore, there is urgency to seek new anti-cancer drugs for the intervention of OSCC.…”

TGF‐β1 and IL‐17A comediate the protumor phenotype of neutrophils to regulate the epithelial‐mesenchymal transition in oral squamous cell carcinoma

“…Immunohistochemistry and immunofluorescence staining were performed as described previously 21 . The detailed procedure is shown in .…”

Mechanisms involved in cancer stem cell resistance in head and neck squamous cell carcinoma

“…Several associations between clinicopathological characteristics and CSCs have been appointed in HNSCC, including tumor size, regional and distant metastases, perineural invasion, radiation failure, and poor disease-free survival [30] . A previous study of our group explored CSCs markers in tongue tumors and found that the overexpression of CD44 was related to worst overall survival, and Nanog and Oct4 were associated with regional metastasis and death [31] . Ma et al suggested that CD133 + cells could be responsible for aggressiveness and chemoresistance in oral tumors [32] .…”