An Updated Review of Oral Cancer Stem Cells and Their Stemness Regulation

Shin, Kihyuk; Kim, Reuben H.

doi:10.1615/critrevoncog.2018027501

Cited by 35 publications

(50 citation statements)

References 158 publications

(165 reference statements)

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“…27,28 Recent studies have uncovered and validated the pathophysiologic role of self-renewing cells, namely, cancer stem cells (CSCs; also known as tumor-initiating cells), in long-term maintenance of cancers. 29 CSCs share many molecular similarities to embryonic and normal adult stem cells. Many molecular determinants of normal stem cells, such as selfrenewal ability and multi-lineage differentiation capacity, are retained in CSCs.…”

Section: Introductionmentioning

confidence: 99%

“…Many molecular determinants of normal stem cells, such as selfrenewal ability and multi-lineage differentiation capacity, are retained in CSCs. 29 CSCs have been isolated from various primary tumors and established cancer cell lines via cell surface markers, and they typically have the following properties: high tumourigenicity upon injection in immunodeficient mice, the ability to grow as tumor spheres in undifferentiating medium and resistance to cancer therapeutic agents. 29 Therefore, CSCs drive the perpetuity of the disease while producing cellular heterogeneity of cancer tissues and are becoming new targets of anticancer therapies.…”

Section: Introductionmentioning

confidence: 99%

“…29 CSCs have been isolated from various primary tumors and established cancer cell lines via cell surface markers, and they typically have the following properties: high tumourigenicity upon injection in immunodeficient mice, the ability to grow as tumor spheres in undifferentiating medium and resistance to cancer therapeutic agents. 29 Therefore, CSCs drive the perpetuity of the disease while producing cellular heterogeneity of cancer tissues and are becoming new targets of anticancer therapies. 29 The phenotypes of CSCs have been reported to be maintained by several endogenous signaling pathways, including Notch, Hedgehog, and Wnt.…”

Section: Introductionmentioning

confidence: 99%

“…29 Therefore, CSCs drive the perpetuity of the disease while producing cellular heterogeneity of cancer tissues and are becoming new targets of anticancer therapies. 29 The phenotypes of CSCs have been reported to be maintained by several endogenous signaling pathways, including Notch, Hedgehog, and Wnt. 30 In addition to the endogenous pathways, CSCs could be enriched by exogenous carcinogenic factors.…”

Section: Introductionmentioning

confidence: 99%

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Proinflammatory cytokine TNFα promotes HPV-associated oral carcinogenesis by increasing cancer stemness

Hong¹,

Akhavan²,

Lee³

et al. 2020

Int J Oral Sci

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High-risk human papillomaviruses (HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α (TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase (hTERT)-immortalized cells. TNFα treatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as (1) calcium resistance, (2) anchorage independence, and (3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in hTERTimmortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated hTERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting microRNAs miR-203 and miR-200c. Overexpression of miR-203 and miR-200c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proinflammatory cytokine TNFα promotes HPV-associated oral carcinogenesis by increasing cancer stemness

Hong¹,

Akhavan²,

Lee³

et al. 2020

Int J Oral Sci

Self Cite

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“…Oral Cancers include many squamous cell carcinomas that may have varying responsiveness to chemotherapy and radiation treatments [1,2]. Recent evidence has demonstrated that a sub-population of oral cancers may be cancer stem cells (CSC), which exhibit cancerous but also stem cell phenotypesincluding chemotherapeutic and radiation resistance [3,4]. Based upon these phenotypes, recent efforts have focused on identifying specific biomarkers to identify tumors with sub-populations of CSC [5,6].…”

Section: Introductionmentioning

confidence: 99%

Differential exosome miRNA expression in oral cancer stem cells

Shoff

Booker

Leavitt

et al. 2020

ExRNA

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Background: Oral squamous cell carcinomas (OSCC) secrete exosomes into the surrounding extracellular environment to promote the horizontal transfer of bioactive molecules including microRNA (miRNA). The primary objective of this study was to explore potential differences in miRNA content between OSCC and OSCC stem cells.Methods: The OSCC cell lines SCC4, SCC15, SCC25 and CAL27 were used in these studies. The corresponding OSCC stem cells that demonstrated phenotypic adhesion independent tumor spheres (AiTS) were manually isolated. All cells were cultured in DMEM containing 10% exosome-free fetal bovine serum. Exosomes were isolated using Total Exosome Isolation reagent (Invitrogen) and RNA was purified using Total Exosome RNA isolation kit (Invitrogen). Exosome miRNA content was evaluated using miRNA Advanced Taqman Assays for miR-21, − 155, − 133, − 34, − 31, − 32, and − 365. The fold change of miRNA content was calculated using the comparative CT (ΔΔCT) method using miR-16 as an endogenous control. Results: After successful cell cultures were established, AiTS (cancer stem cells) were manually separated and confirmed using CD133 and Sox-2 biomarkers. Exosomes and extracellular vesicles were successfully isolated from all cell lines and AiTS isolates for miRNA screening. All isolates exhibited miR-16 expression (positive control), but none contained mir-31, − 32, or 133a. Differential expression of miR-21, miR-34 and miR-155 were observed with patterns observed among the cancer cell lines which were distinct from the corresponding AiTS isolates. Conclusions: Exosomes isolated from these different OSCC stem cell populations displayed nearly consistent downregulation/loss of miR-21 and miR-34 suggesting the possibility of a unique miRNA profile characteristic of oral cancer stem cells. These findings highlight the need to investigate the comprehensive functions of miR-21 and miR-34 in tumor progression and continued research to refine a miRNA profile that could aid in distinguishing tumors with poor prognosis.

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