Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading cause...Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis.Studies have explored the influence of ER stress on OvCa in recent years,while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored.Here,we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)cohorts for the screening of prognosis-related genes.The least absolute shrinkage and selection operator(LASSO)regression was applied to establish an ER stress-related risk signature based on the TCGA cohort.A seven-gene signature revealed a favorable predictive efficacy for the TCGA,International Cancer Genome Consortium(ICGC),and another GEO cohort(P<0.001,P<0.001,and P=0.04,respectively).Moreover,functional annotation indicated that this signature was enriched in cellular response and senescence,cytokines interaction,as well as multiple immune-associated terms.The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group.In conclusion,ER stress-related genes are vital factors predicting the prognosis of OvCa,and possess great application potential in the clinic.展开更多
There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSC...There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSCs existed in human ovarian cancer (OVCA) cell line and whether anti-CD44 antibody had effects on such subpopulation. We isolated and identified spheroid cells from SKOV-3. Then we used A3D8, an anti-CD44 mAb to treat spheroid cells with so-called "stemness". Effects of A3D8 on spheroid cells' biological behaviors were examined. Our findings showed that there was a small subpopulation that had so-called "stemness" in SKOV-3 cell line. Against spheroid cells, A3D8 can (1) inhibit cell proliferation; (2) change cell cycle distribution and expression of p21, CDK2 and cyclinA; (3) enhance cisplatin (DDP)-induced apoptosis; (4) promote cell differentiation; (5) inhibit clone formation efficiency; (6) reduce invasive efficacy; (7) inhibit tumorigenicity. Thus, to sum up points which we have just showed, spheroid cells isolated from SKOV-3 can be used as an appropriate in vitro model for relevant study of human ovarian CSCs. And our results reasoned that anti-CD44 therapy may become a potential promising strategy for OVCA treatment.展开更多
目的:探讨卵巢癌基因1[ovarian cancer gene 1,OVCA1;也称为DPH2L(diphthamide synthesis protein 2-like)基因]体外对卵巢癌细胞系A2780迁移和侵袭能力的抑制作用。方法:采用脂质体法将GFP标记的携带OVCA1的重组质粒 pEGFP-OVCA1或GFP...目的:探讨卵巢癌基因1[ovarian cancer gene 1,OVCA1;也称为DPH2L(diphthamide synthesis protein 2-like)基因]体外对卵巢癌细胞系A2780迁移和侵袭能力的抑制作用。方法:采用脂质体法将GFP标记的携带OVCA1的重组质粒 pEGFP-OVCA1或GFP空白质粒分别转染A2780细胞后,G418筛选稳定转染细胞,有限稀释法筛选稳定转染细胞的单克隆细胞株,荧光显微镜检查绿色荧光蛋白的表达及RT-PCR方法检测A2780细胞OVCA1基因mRNA的表达。A2780-OVCA1细胞为实验组,A2780-GFP细胞和A2780细胞为对照组,采用划痕实验、Transwell体外迁移实验和Matrigel体外侵袭实验检测 OVCA1对A2780细胞迁移和侵袭能力的影响。结果:重组质粒pEGFP-OVCA1转染后获得了稳定表达GFP标记OVCA1蛋白的A2780细胞株。A2780-OVCA1组划痕后的细胞迁移速度明显小于两对照组(P<0.05);A2780-OVCA1组穿过Transwell 滤膜的迁移细胞数明显少于两对照组(P<0.05);A2780-OVCA1组穿过Matrigel滤膜的侵袭细胞数明显少于两对照组(P< 0.05)。结论:OVCA1在体外具有显著抑制卵巢癌A2780细胞迁移和侵袭的作用。展开更多
基金This work was supported by the Shanghai Shenkang Hospital Development Center’s Shenkang Promotion of Clin‑ical Skills and Clinical Innovation in Municipal Hospitals Three-Year Action Plan(No.2020‒2023)the Major Clinical Research Project(No.SHDC2020CR1048B)the Pilot Construction Project of High-Level Universities in Shanghai(No.DGF501017-06),China。
文摘Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis.Studies have explored the influence of ER stress on OvCa in recent years,while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored.Here,we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)cohorts for the screening of prognosis-related genes.The least absolute shrinkage and selection operator(LASSO)regression was applied to establish an ER stress-related risk signature based on the TCGA cohort.A seven-gene signature revealed a favorable predictive efficacy for the TCGA,International Cancer Genome Consortium(ICGC),and another GEO cohort(P<0.001,P<0.001,and P=0.04,respectively).Moreover,functional annotation indicated that this signature was enriched in cellular response and senescence,cytokines interaction,as well as multiple immune-associated terms.The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group.In conclusion,ER stress-related genes are vital factors predicting the prognosis of OvCa,and possess great application potential in the clinic.
基金supported by the National Natural Science Foundation of China (30670801)the Tianjin Research Program of Application Foundation and Advanced Technology (06YFJMJC08300)
文摘There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSCs existed in human ovarian cancer (OVCA) cell line and whether anti-CD44 antibody had effects on such subpopulation. We isolated and identified spheroid cells from SKOV-3. Then we used A3D8, an anti-CD44 mAb to treat spheroid cells with so-called "stemness". Effects of A3D8 on spheroid cells' biological behaviors were examined. Our findings showed that there was a small subpopulation that had so-called "stemness" in SKOV-3 cell line. Against spheroid cells, A3D8 can (1) inhibit cell proliferation; (2) change cell cycle distribution and expression of p21, CDK2 and cyclinA; (3) enhance cisplatin (DDP)-induced apoptosis; (4) promote cell differentiation; (5) inhibit clone formation efficiency; (6) reduce invasive efficacy; (7) inhibit tumorigenicity. Thus, to sum up points which we have just showed, spheroid cells isolated from SKOV-3 can be used as an appropriate in vitro model for relevant study of human ovarian CSCs. And our results reasoned that anti-CD44 therapy may become a potential promising strategy for OVCA treatment.
