BackgroundCancer stem cells (CSCs) play an important role in tumor initiation, progression, and metastasis and are responsible for high therapeutic failure rates. Identification and characterization of CSC are crucial for facilitating the monitoring, therapy, or prevention of cancer. Great efforts have been paid to develop a more effective methodology. Nevertheless, the ideal model for CSC research is still evolving. In this study, we created a nonadhesive culture system to enrich CSCs from human oral squamous cell carcinoma cell lines with sphere formation and to characterize their CSC properties further.MethodsA nonadhesive culture system was designed to generate spheres from the SAS and OECM-1 cell lines. A subsequent investigation of their CSC properties, including stemness, self-renewal, and chemo- and radioresistance in vitro, as well as tumor initiation capacity in vivo, was also performed.ResultsSpheres were formed cost-effectively and time-efficiently within 5 to 7 days. Moreover, we proved that these spheres expressed putative stem cell markers and exhibited chemoradiotherapeutic resistance, in addition to tumor-initiating and self-renewal capabilities.ConclusionsUsing this nonadhesive culture system, we successfully established a rapid and cost-effective model that exhibits the characteristics of CSCs and can be used in cancer research.

Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. The prognosis of HNSCC is usually poor because of its propensity for extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Carcinoma-associated fibroblasts (CAFs), a major type of tumour-surrounding stromal cell, generate mediators through which they interact with tumours and contribute to cancer progression. The orchestration between CAFs and cancer cells is complex. Despite recent studies demonstrating the paracrine effect of stromal cells in the tumour microenvironment on initiation and progression of cancer cells, the major mediator related to CAFs and its underlying mechanism remain unknown. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behaviour of HNSCC cells. Using microarray analysis, we detected abundant expression of interleukin-33 (IL-33) in CAFs and identified IL-33 as a critical mediator in CAF-induced invasiveness. Counteracting IL-33 activity diminished the aggressive phenotype of cancer cells induced by CAFs. Administration of IL-33 promoted cancer cell migration and invasion through induction of epithelial-to-mesenchymal transdifferentiation and increased IL-33 gene expression in cancer cells. In 40 patients with HNSCC, IL-33 expression in CAFs correlated with IL-33 expression in cancer cells. Most cases with a low invasion pattern grading score (IPGS) showed low or no expression of IL-33, whereas most HNSCC cases with high IPGS displayed over-expression of IL-33 in CAFs and cancer cells. High IL-33 expression associated with poor prognosis in terms of nodal metastasis-free survival. These results indicate that CAFs promote cancer invasiveness via paracrine and autocrine effects on microenvironmental IL-33 signalling, and suggest that IL-33 is a potential prognostic biomarker that could be considered in therapeutic strategies for the treatment of patients with HNSCC.

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Mulberry (Morus alba L.) has been considered to possess different benefits such as protecting liver; improving fever, urine excretion disorder, hypertension, and diabetic syndrome; and preventing cardiovascular diseases. Recently, mounting evidence has shown that mulberry anthocyanin extract (MAE) is beneficial to hyperlipidemia; however, the mechanisms remain unclear. The present study was aimed to investigate the protective effects of MAE on hepatocyte cultured with high fatty acid and the underlying mechanisms. By using human hepatoma cell HepG2 as cell model, the results showed that MAE suppressed fatty acid synthesis and enhanced fatty acid oxidation, contributing to amelioration of lipid accumulation induced by oleic acid (OA). Moreover, MAE also inhibited acetyl coenzyme A carboxylase (ACC) activities by stimulating adenosine monophosphate-activated protein kinase (AMPK). MAE attenuated the expression of sterol regulatory element-binding protein-1 (SREBP-1) and its target molecules, such as fatty acid synthase (FAS). Similar results were also found in the expressions of enzymes involved in triglyceride and cholesterol biosyntheses including glycerol-3-phosphate acyltransferase (GPAT), 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCoR), adipocyte-specific fatty acid binding protein (A-FABP), and SREBP-2. In contrast, the lipolytic enzyme expressions of peroxisome proliferator activated receptor α (PPARα) and carnitinepalmitol- transferase-1 (CPT1) were increased. This study suggests the hypolipidemic effects of MAE occur via phosphorylation of AMPK and inhibition of lipid biosynthesis and stimulation of lipolysis. Therefore, the mulberry anthocyanins may actively prevent nonalcoholic fatty liver disease.