Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma

Background/Aims: Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined. Methods: Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and β-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and β-catenin were used to inhibit autophagy and β-catenin signaling pathway, respectively, as loss-of-function experiments. Results: We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced β-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on β-catenin and cell viability, while increasing β-catenin abolished the effects of GRh2 on autophagy and cell viability. Conclusion: Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and β-catenin signaling.

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Different Aspects of Head and Neck Squamous Cell Carcinoma: Cancer Stem Cells, Their Niche and Targeted Therapy

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200921163326 ◽

2020 ◽

Vol 15 ◽

Author(s):

Meriç Bilgiç Küçükgüven ◽

Betül Çelebi-Saltik

Keyword(s):

Stem Cells ◽

Squamous Cell Carcinoma ◽

Targeted Therapy ◽

Cancer Stem Cells ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Crucial Role ◽

Tumor Therapy ◽

Neck Squamous Cell Carcinoma

: Head and Neck Squamous Cell Carcinoma (HNSCC) is categorized as the sixth most common cancer worldwide, with an incidence of more than 830,000 cases per year and a mortality rate of 50%. Tobacco use, alcohol consumption, and Human Papillomavirus infection are the prominent risks for HNSCC. Despite significant developments in the treatment of HNSCC, a high rate of recurrences makes the clinical situation worse and results in poor survival rates. Recent perspectives demonstrate that whereas epithelial transformation plays a crucial role in cancer development, tumor surrounding microenvironment takes part in progression of cancer as well. Cancer Stem Cells (CSCs), which harbor unlimited self-renewal capacity, have a crucial role in the growth of HNSCC and this cell population is responsible for tumor recurrence unless eliminated by targeted therapy. CSCs are not only a promising target for tumor therapy, but also a crucial biomarker to determine the patients at high risk for undetermined results and disease development. Just as the bone marrow which is the niche of hematopoietic and mesenchymal stem cells, is important for stem cells maintenance. Similarly, the concept of microenvironment is also important for the maintenance of CSCs. Apart from the cell-cell interactions, there are many parameters in the cancer microenvironment that affect the development of cancer, such as extracellular regulation, vascularization, microbial flora, pH and oxygenation. The purpose of this review is to introduce HNSCC, explain the role of CSCs and their microenvironment and refer to the conventional and novel targeted therapy for HNSCC and CSCs.

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Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells

British Journal of Cancer ◽

10.1038/s41416-021-01499-3 ◽

2021 ◽

Author(s):

Zhigeng Zou ◽

Wei Zheng ◽

Hongjun Fan ◽

Guodong Deng ◽

Shih-Hsin Lu ◽

...

Keyword(s):

Stem Cells ◽

Squamous Cell Carcinoma ◽

Cancer Stem Cells ◽

Cell Carcinoma ◽

Cell Lines ◽

Squamous Cell ◽

High Throughput Sequencing ◽

Combined Treatment ◽

Oesophageal Squamous Cell Carcinoma

Abstract Background Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. Methods We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. Results ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. Conclusions ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.

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