Diversity of the Origin of Cancer Stem Cells in Oral Squamous Cell Carcinoma and Its Clinical Implications

Abstract

Oral squamous cell carcinoma (OSCC) histopathologically accounts for ≥90% of oral cancer. Many clinicopathological risk factors for OSCC have also been proposed, and postoperative therapy is recommended in guidelines based on cancer stage and other risk factors. However, even if the standard treatment is provided according to the guidelines, a few cases rapidly recur or show cervical and distant metastasis. In this review article, we focus on the diversity of the origin of OSCC. We also discuss cancer stem cells (CSCs) as a key player to explain the malignancy of OSCC. CSCs are a subset of cancer cells that occupy a very small portion of the cancer mass and have characteristics of stem cells. When gene abnormalities accumulate in somatic stem cells, those cells transform into CSCs. CSCs as the origin of cancer then autonomously grow and develop into cancer. The histopathological phenotype of cancer cells is determined by the original characteristics of the somatic stem cells and/or surrounding environment. OSCC may be divided into the following three categories with different malignancy based on the origin of CSCs: cancer from oral epithelial stem cell-derived CSCs, cancer from stem cells in salivary gland-derived CSCs, and cancer from bone marrow-derived stem cell-derived CSCs.

Expression of the Embryonic Cancer Stem Cells’ Biomarkers SOX2 and OCT3/4 in Oral Leukoplakias and Squamous Cell Carcinomas: A Preliminary Study

“…CSCs seem to play an important role in the initiation and development of various malignancies [ 29 - 31 ]. The detection of CSCs in solid cancers was firstly confirmed in 2003, by Al-Hajj et al, who showed that only a fraction of CD44+/CD24+ or negative breast cancer cells could create a tumor with the same characteristics of the initial tumor [ 32 ].…”

The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

“…They may also be a valuable biomarker to detect HNC patients with resistance to therapy or a high risk of tumor recurrence [ 7 , 72 ]. CSCs have been identified as a small population of cancer cells in tumor tissue in terms of 0.01–2% of total tumor mass that have similar features to embryonic and normal stem cells [ 6 , 73 ]. CSCs have asymmetrical cell division and self-renewal capability, which induce a heterogeneous subpopulation of cancer cells involved in angiogenesis and immortality [ 6 , 7 , 73 ].…”

“…CSCs have been identified as a small population of cancer cells in tumor tissue in terms of 0.01–2% of total tumor mass that have similar features to embryonic and normal stem cells [ 6 , 73 ]. CSCs have asymmetrical cell division and self-renewal capability, which induce a heterogeneous subpopulation of cancer cells involved in angiogenesis and immortality [ 6 , 7 , 73 ]. It is well known that CSCs are more malignant than other subsets of cancer cells in tumor masses.…”

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

“…CSCs activity is modulated by different signals and cellular interactions provided by the tumor microenvironment, allowing CSCs to achieve highly invasive and aggressive behavior or resist conventional therapies. Thus, activating the Epithelial-to-Mesenchymal Transition (EMT) program by the CSCs represents a valuable strategy to promote invasion, metastasis, and treatment resistance [10][11][12] .…”

“…CSCs may originate from adult stem cells or progenitor cells in which the accumulation of mutations over time leads to the activation of transcriptional gene signatures and signaling pathways related to the maintenance of stem cell phenotype and malignant transformation [ 13 - 15 ] . Moreover, differentiated cells can also acquire stemness traits due to genetic instability throughout their division process and dedifferentiate, acquiring stem cell properties [ 16 , 17 ] .…”