The context-dependent reciprocal interaction between the cancer cells and surrounding fibroblasts is imperative for regulating malignant potential,metabolic reprogramming,immunosuppression,and ECM deposition.However,r...The context-dependent reciprocal interaction between the cancer cells and surrounding fibroblasts is imperative for regulating malignant potential,metabolic reprogramming,immunosuppression,and ECM deposition.However,recent evidence also suggests that cancer-associated fibroblasts induce chemoresistance in cancer cells to various anticancer regimens.Because of the protumorigenic function of cancer-associated fibroblasts,these stromal cell types have emerged as fascinating therapeutic targets for cancer.However,this notion was recently challenged by studies that targeted cancer-associated fibroblasts and highlighted the underlying heterogeneity by identifying a subset of these cells with tumor-restricting functions.Hence,it is imperative to understand the heterogeneity and heterotypic signaling of cancer-associated fibroblasts to target tumor-promoting signaling processes by sparing tumor-restricting ones.In this review,we discuss the heterogeneity and heterotypic signaling of cancer-associated fibroblasts in shaping drug resistance and also list the cancer-associated fibroblast-targeting therapeutics.展开更多
目的探讨膀胱尿路上皮癌中MHCI类链相关蛋白A（MHC class I chain．relatedA，MICA）的表达，以及与核因子-KB（ntlclear factor-κB，NF—κB）和p53的相互关系，为研究膀胱癌组织中MICA蛋白的表达机制提供组织学依据。方法用免疫组化...目的探讨膀胱尿路上皮癌中MHCI类链相关蛋白A（MHC class I chain．relatedA，MICA）的表达，以及与核因子-KB（ntlclear factor-κB，NF—κB）和p53的相互关系，为研究膀胱癌组织中MICA蛋白的表达机制提供组织学依据。方法用免疫组化方法检测75例膀胱尿路上皮癌及15例正常膀胱黏膜中MICA、NF-κB和p53蛋白表达，对MICA、NF-κB和p53在正常膀胱黏膜、浸润和非浸润膀胱癌中的表达进行统计学分析。结果（1）MICA、NF—κB和p53蛋白在膀胱癌的表达率分别为48．0％、85．3％和49．3％，均显著高于正常膀胱黏膜（P〈0．05）。MICA蛋白在浸润性膀胱癌的表达低于非浸润性膀胱癌（P〈0．05）。（2）膀胱癌组织中MICA与NF-κB蛋白表达呈正相关（r=0．256，P=0．027），而MICA和p53蛋白的表达呈负相关（r=-0．23，P=0．047）。结论膀胱癌中MICA蛋白常表达上调，可作为膀胱癌的肿瘤相关抗原；NF-κB通路可能参与MICA的表达调控；p53通路可能不参与膀胱尿路上皮恶性转化过程中MICA蛋白的表达。展开更多
文摘The context-dependent reciprocal interaction between the cancer cells and surrounding fibroblasts is imperative for regulating malignant potential,metabolic reprogramming,immunosuppression,and ECM deposition.However,recent evidence also suggests that cancer-associated fibroblasts induce chemoresistance in cancer cells to various anticancer regimens.Because of the protumorigenic function of cancer-associated fibroblasts,these stromal cell types have emerged as fascinating therapeutic targets for cancer.However,this notion was recently challenged by studies that targeted cancer-associated fibroblasts and highlighted the underlying heterogeneity by identifying a subset of these cells with tumor-restricting functions.Hence,it is imperative to understand the heterogeneity and heterotypic signaling of cancer-associated fibroblasts to target tumor-promoting signaling processes by sparing tumor-restricting ones.In this review,we discuss the heterogeneity and heterotypic signaling of cancer-associated fibroblasts in shaping drug resistance and also list the cancer-associated fibroblast-targeting therapeutics.
文摘目的探讨膀胱尿路上皮癌中MHCI类链相关蛋白A（MHC class I chain．relatedA，MICA）的表达，以及与核因子-KB（ntlclear factor-κB，NF—κB）和p53的相互关系，为研究膀胱癌组织中MICA蛋白的表达机制提供组织学依据。方法用免疫组化方法检测75例膀胱尿路上皮癌及15例正常膀胱黏膜中MICA、NF-κB和p53蛋白表达，对MICA、NF-κB和p53在正常膀胱黏膜、浸润和非浸润膀胱癌中的表达进行统计学分析。结果（1）MICA、NF—κB和p53蛋白在膀胱癌的表达率分别为48．0％、85．3％和49．3％，均显著高于正常膀胱黏膜（P〈0．05）。MICA蛋白在浸润性膀胱癌的表达低于非浸润性膀胱癌（P〈0．05）。（2）膀胱癌组织中MICA与NF-κB蛋白表达呈正相关（r=0．256，P=0．027），而MICA和p53蛋白的表达呈负相关（r=-0．23，P=0．047）。结论膀胱癌中MICA蛋白常表达上调，可作为膀胱癌的肿瘤相关抗原；NF-κB通路可能参与MICA的表达调控；p53通路可能不参与膀胱尿路上皮恶性转化过程中MICA蛋白的表达。
