Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Can...Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and selfrenewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD133, have been of great interest. CD133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of CD133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of CD133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of CD133 in colorectal cancers. In addition, we focus on the prognostic value of CD133 in colorectal cancers. Finally, we predict that CD133 may be used as a possible target for colorectal cancer treatment.展开更多
AIM To determine the potential roles of CD4 and micro RNA(mi R)-145 in gastric cancer.METHODS The levels of CD44 and mi R-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction w...AIM To determine the potential roles of CD4 and micro RNA(mi R)-145 in gastric cancer.METHODS The levels of CD44 and mi R-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 m RNA. A luciferase reporter assay and western blotting were performed to examine the effect of mi R-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells.RESULTS The expression of CD44 was greatly increased and mi R-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells(CSCs). The results demonstrated that mi R-145 regulated CD44 by targeting directly the CD44 3'-untranslated region(3'-UTR). In gastric cancer cells, overexpression of mi R-145 repressed the activity of the CD44 3'-UTR, and disruption of mi R-145/CD44 3'-UTR interactions abrogated the silencing effects. In addition, mi R-145 inhibition stimulated CD44 3'-UTR activity and disruption of mi R-145/CD44 3'-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemoresistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with mi R-145 were significantly abrogated by overexpression of CD44. CONCLUSION mi R-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.展开更多
Background and Objective:Chemotherapy is the main treatment for colon cancer,while multidrugresistance is the main reason for chemotherapy failure and tumor relapse.This study was to establish two oxaliplatinresistant...Background and Objective:Chemotherapy is the main treatment for colon cancer,while multidrugresistance is the main reason for chemotherapy failure and tumor relapse.This study was to establish two oxaliplatinresistant colon cancer cell lines and evaluate their biological characteristics.Met hods:Oxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin(L-OHP) of low and gradually increased concentration.Growth curve,cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay.The expressions of P-glycoprotein(P-gp),multidrugresistance protein 1(MRP1) and MRP2 were detected by Western blot.Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry.Result s:It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin.Cross-resistance to 5-fluorouracil,etoposide,cisplatin,vincristine and epirubicin but not to paclitaxel was observed.Longer doubling time,higher proportion of cells in G0/G1 phase and lower proportion in G2/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines.The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated,while those of P-gp and MRP1 had no significant change.CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells.Conclusions:SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.展开更多
背景:肿瘤干细胞与肿瘤的复发、转移以及耐药等之间存在十分密切的联系。目的:探讨CD44^+CD24^(-/low)乳腺癌干细胞活性与多药耐药的相关性。方法:运用免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选出CD44^+CD24^(-/low)乳腺癌干细...背景:肿瘤干细胞与肿瘤的复发、转移以及耐药等之间存在十分密切的联系。目的:探讨CD44^+CD24^(-/low)乳腺癌干细胞活性与多药耐药的相关性。方法:运用免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选出CD44^+CD24^(-/low)乳腺癌干细胞。流式细胞仪测定分选后CD44^+CD24^(-/low)乳腺癌干细胞亚群比例和细胞膜P-gp荧光强度,RT-PCR法检测多药耐药基因MDR m RNA表达水平。结果与结论:(1)获得的CD44^+CD24^(-/low)乳腺癌干细胞比例在90%以上;(2)CD44^+CD24^(-/low)细胞亚群成球比例明显强于non-CD44^+CD24^(-/low)细胞亚群;(3)CD44^+CD24^(-/low)细胞亚群的细胞膜P-gp荧光强度显著高于MFC-7/ADR细胞株(P<0.05);(4)CD44^+CD24^(-/low)细胞亚群的MDR mRNA表达水平显著高于MFC-7/ADR细胞株(P<0.05);(5)结果表明,分选得到的CD44^+CD24^(-/low)乳腺癌干细胞具有很强的体外成球能力,高表达P-gp蛋白和MDR mRNA可能是导致多药耐药的原因之一。展开更多
基金Supported by Clinical Key Discipline Fund by Ministry of Health(2010-2012)Chinese National Clinical Key Discipline(2011-2012)the Shanghai Science and Technology Commission of Shanghai Municipality,No.10DJ1400500
文摘Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and selfrenewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD133, have been of great interest. CD133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of CD133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of CD133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of CD133 in colorectal cancers. In addition, we focus on the prognostic value of CD133 in colorectal cancers. Finally, we predict that CD133 may be used as a possible target for colorectal cancer treatment.
基金Supported by Quanzhou excellent personnel training,No.10A16Natural Science Foundation of Fujian Province,No.JA08084Fujian Medical University,No.092D014
文摘AIM To determine the potential roles of CD4 and micro RNA(mi R)-145 in gastric cancer.METHODS The levels of CD44 and mi R-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 m RNA. A luciferase reporter assay and western blotting were performed to examine the effect of mi R-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells.RESULTS The expression of CD44 was greatly increased and mi R-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells(CSCs). The results demonstrated that mi R-145 regulated CD44 by targeting directly the CD44 3'-untranslated region(3'-UTR). In gastric cancer cells, overexpression of mi R-145 repressed the activity of the CD44 3'-UTR, and disruption of mi R-145/CD44 3'-UTR interactions abrogated the silencing effects. In addition, mi R-145 inhibition stimulated CD44 3'-UTR activity and disruption of mi R-145/CD44 3'-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemoresistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with mi R-145 were significantly abrogated by overexpression of CD44. CONCLUSION mi R-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.
基金National Natural Science Foundation of China (No. 30901719,No.30971519)
文摘Background and Objective:Chemotherapy is the main treatment for colon cancer,while multidrugresistance is the main reason for chemotherapy failure and tumor relapse.This study was to establish two oxaliplatinresistant colon cancer cell lines and evaluate their biological characteristics.Met hods:Oxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin(L-OHP) of low and gradually increased concentration.Growth curve,cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay.The expressions of P-glycoprotein(P-gp),multidrugresistance protein 1(MRP1) and MRP2 were detected by Western blot.Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry.Result s:It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin.Cross-resistance to 5-fluorouracil,etoposide,cisplatin,vincristine and epirubicin but not to paclitaxel was observed.Longer doubling time,higher proportion of cells in G0/G1 phase and lower proportion in G2/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines.The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated,while those of P-gp and MRP1 had no significant change.CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells.Conclusions:SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.
文摘背景:肿瘤干细胞与肿瘤的复发、转移以及耐药等之间存在十分密切的联系。目的:探讨CD44^+CD24^(-/low)乳腺癌干细胞活性与多药耐药的相关性。方法:运用免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选出CD44^+CD24^(-/low)乳腺癌干细胞。流式细胞仪测定分选后CD44^+CD24^(-/low)乳腺癌干细胞亚群比例和细胞膜P-gp荧光强度,RT-PCR法检测多药耐药基因MDR m RNA表达水平。结果与结论:(1)获得的CD44^+CD24^(-/low)乳腺癌干细胞比例在90%以上;(2)CD44^+CD24^(-/low)细胞亚群成球比例明显强于non-CD44^+CD24^(-/low)细胞亚群;(3)CD44^+CD24^(-/low)细胞亚群的细胞膜P-gp荧光强度显著高于MFC-7/ADR细胞株(P<0.05);(4)CD44^+CD24^(-/low)细胞亚群的MDR mRNA表达水平显著高于MFC-7/ADR细胞株(P<0.05);(5)结果表明,分选得到的CD44^+CD24^(-/low)乳腺癌干细胞具有很强的体外成球能力,高表达P-gp蛋白和MDR mRNA可能是导致多药耐药的原因之一。
