Objective To analyze the advances of cancer stem cell (CSC) in recent years, and to propose a prospect for CSC research and cancer therapy. Methods Articles about important advances of CSC theory and cancer therapy were reviewed, and then selected and summarized. Results In 2001, CSC was first put forward as a concept, till now, which has been confirmed in many tissues. In recent years, efforts were dedicated to such topics including: identification of CSC in sol id tumors, the origin of CSC, its niche and growth mechanism, cancer therapy, etc. According to the CSC theory, traditional therapeutic methods have deficiencies, and new treatment targeting CSC may thoroughly el iminate tumors. Conclusion At present, CSC theory is still controversial, while it proposed revolutionary methods and directions for the therapy of cancer.
Tumor cells have unique energy metabolism phenomena, namely high glucose absorption, aerobic glycolysis and high lactic acid production, which are characterized by down-regulation of related proteins involved in oxidative metabolism in tumor cells, and up-regulation of glucose transporters and monocarboxylate transporters. Studies have shown that drugs that target tumor cell glucose metabolism have the ability to selectively kill tumor cells, bringing new hope for tumor treatment. Tumor stem cells are considered to be the root cause of tumor recurrence, metastasis and poor prognosis, and their energy metabolism characteristics have not yet been agreed. Studies have shown that reversing the energy metabolism of tumor stem cells can increase their chemosensitivity. This article reviews recent studies on tumor and tumor stem cell glucose metabolism and the opportunities and challenges of tumor treatment through targeting glucose metabolism, which might provide new ideas and opportunities for clinical tumor therapy.
ObjectiveTo explore the expression of genes related to hepatocellular carcinoma (HCC) stem cells and their prognostic correlation by using weighted gene co-expression network analysis (WGCNA).MethodsFirstly, the transcriptome sequencing (RNA-seq) and clinical data of HCC were downloaded from the public database the Cancer Genome Atlas (TCGA), and the mRNA expression-based stiffness index (mRNAsi) table of cancer stem cells was downloaded and sorted out to analyze the relationship between mRNAsi and pathological grade and prognosis of HCC. The mRNAsi of HCC was downloaded and the prognostic value of mRNAsi was discussed. Then we used WGCNA to screen the key modules related to liver cancer stem cells (LSCS). Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used for the functional and pathway enrichment analysis. The online database STRING was used to construct hub genes coding proteins interaction (PPI) network and screen key genes. Finally, the key genes were analyzed for expression differences and expression correlations. The online database Kaplan-Meier plotter was used for survival analysis and verified.ResultsmRNAsi was significantly upregulated in cancer tissues (P<0.001), and increased with the increase of pathological grade of HCC (P=0.001). The mortality rate of the higher mRNAsi group was higher than that of the lower mRNAsi group (P=0.006). GO analysis found that hub genes were mainly involved in biological processes, such as mitosis and DNA replication, and KEGG showed that hub genes were enriched in cell cycle, DNA mismatch repair, oocyte meiosis, and other signaling pathways. We screened 10 key genes (included CCNB1, CDC20, CDCA8, NDC80, KIF20A, TTK, CDC45, KIF15, MCM2, and NCAPG) related to mRNAsi of HCC based on WGCNA. The key genes were highly expressed in the tumor samples compared to the normal samples. In addition, there was a strong interaction between proteins of these key genes (P<0.05), a strong co-expression relationship at the transcriptional level, and all related to prognosis of HCC.ConclusionsmRNAsi plays an important role in the occurrence and development of HCC. Ten key genes related to LSCS were screened, which may act as therapeutic targets for inhibiting the stem cell characteristics of HCC.
ObjectiveTo investigate the most appropriate culture time with the action of EGF in colon cancer stem cells enrichment by suspension culture.MethodsDLD-1 cells were cultured in serum-free medium containing 20 ng/mL EGF to generate spheroid cells. The time gradient was set to 10 d, 20 d, 30 d and 40 d, the cell proportion of CD133+, CD44+ and CD133+CD44+ were confirmed by flow cytometery. The ability of self-renewal was detected by the sphere forming assay and the limited dilution assay, and the in vitro tumorigenicity of the cells was detected by the colony formation assay.ResultsIn the 30 d group, the proportion of CD133+ and CD133+ CD44+ cells were significantly higher than those in the other groups (allP<0.05), the CD44+ cell was higher than that in the 20 d group (P<0.05), but there was no significant difference with the other two groups (P>0.05). The results of the limited dilution assay and the colony formation assay, the number of spheres in the 30 d or 40 d group was the highest among the 4 groups, and there was no statistical difference between the 30 d group and 40 d group (P>0.05), with statistically significant difference between the 30 d, 10 d and 20 d groups (all P<0.05). The results of the sphere forming assay and the self-renewal ability of 30 d group was significantly higher compared with other groups (all P< 0.05).ConclusionThe cancer stem cells could be enriched more efficiently by suspension culture using 20 ng/mL EGF for 30 days.
Objective To investigate the clinical outlook of hepatic stem cells and its relations with liver cancer. Methods The literatures of recent years on the studies of hepatic stem cells were reviewed. Results Liver cancer may consist of cells of various differentiation grades and it may result from the perodifferentiated hepatic stem cells or abnormal differentiated cells. Conclusion The hypothesis of hepatic stem cells has been identified extensively. Further study maybe helpful for revealing the origin, carcinogenesis of hepatic cancer, and may also be useful for the understanding of the mechanism of metastasis.
ObjectiveTo summarize the role of epithelial-mesenchymal-transition （EMT） in occurrence and development of gastrointestinal cancer. MethodsDomestic and international publications online involving EMT of gastrointestinal cancer in recent years were collected and reviewed. ResultsEMT was a highly conserved process that has been well characterised in embryogenesis. Studies had shown that the aberrant activation of EMT in adult epithelia could promote tumour metastasis by repressing cell adhesion molecules. E-cadherin， one of the epithelial cell markers, maybe involved in the process of the EMT, especially of the Ecadherin transcriptional repressors， these transcriptional repressors significantly increased in the gastrointestinal cancer. Further more， EMT might involve in the process of gastrointestinal cancer stem cells formation. ConclusionsEMT and it’s regulators play a very important role in gastrointestinal cancer， and may provide a newsight into the gastrointestinal cancer. It also can provide a novel clinical targets to treat the gastrointestinal cancer.
Increasing evidence suggests that many types of cancers contain a population of cells that display stem cell properties. These cells are called cancer stem cells （CSCs），which are closely related to tumor initiation，growth，metastasis and chemoresistance. CSCs are also found in esophageal squamous cell carcinoma （ESCC）. These cells are characterized by potential of self-renewal and differentiation，tumor formation in nude mice and chemotherapy resistance，and thus may play an important role in targeted cancer therapies. Current methods for culturing and sorting CSCs in ESCC mainly include fluorescence activated cell sorting （FACS），magnetic activated cell sorting （MACS），suspension culture，and side population （SP） cell sorting. In this review，we focus on current research methods for CSCs in ESCC，their biological characteristics and areas for improvement. We believe that a combination of multiple cell-surface makers is needed for research of CSCs in ESCC.