文章摘要
IGFBP3通过癌旁脂肪细胞促进肾癌细胞生长与转移的作用研究
IGFBP3 Enhances Proliferation and Migration Capability of Renal Carcinoma Cell via Adjacent Adipocytes
投稿时间:2020-05-29  修订日期:2020-05-30
DOI:
中文关键词: IGFBP3  脂代谢  脂肪细胞  肾细胞癌
英文关键词: IGFBP3  lipid metabolism  adipocyte  renal cell carcinoma
基金项目:申康医院研究发展中心(SHDC12014215)
作者单位E-mail
沈梦君 上海交通大学附属第一人民医院泌尿外科 上海 中国 mjsh1123@163.com 
董凯 海军军医大学 上海 中国  
韩厦 上海交通大学附属第一人民医院泌尿外科 上海 中国  
赵宇阳 上海交通大学附属第一人民医院泌尿外科 上海 中国  
徐东亮△ 上海交通大学附属第一人民医院泌尿外科 上海 中国
海军军医大学附属长征医院泌尿外科 上海 中国 
urologistdlx@126.com 
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中文摘要:
      目的:探讨肾透明细胞癌的分泌蛋白IGFBP3对癌旁脂肪细胞分化的作用及通过脂肪细胞促进肾透明癌细胞生长与转移的作用。方法:通过肾细胞癌的基因数据库发现过表达的基因IGFBP3,在标本中确认IGFBP3的表达。分别从基因及蛋白水平检测IGFBP3对原代脂肪细胞分化的影响。以过表达IGFBP3的786-O细胞为模型,检测IGFBP3与TGFβ信号通路的关系。将过表达IGFBP3的786-O细胞与脂肪细胞共培养得到条件培养基,通过油红染色检测条件培养的肾癌细胞中脂滴含量,迁移实验和CCK8实验分别检测脂肪细胞对肾癌细胞侵袭性及增殖的影响。结果:相较于正常组,肾癌标本中IGFBP3的表达增加(P<0.05)。IGFBP3能够促进了前脂肪细胞的分化,这一过程中TGFβ通路激活,p-smad1/5/8、p-p38MAPK表达增加(P<0.05)。条件培养后的786-O细胞内的脂滴形成增加,脂肪细胞促进786-O细胞的增殖和侵袭力。结论:IGFBP3是肾透明细胞癌中过度表达的蛋白,能够促进前脂肪细胞分化,其机制主要通过激活TGFβ通路中的smad1/5/8、p38MAPK。成熟的脂肪细胞能够促进肾癌细胞质脂滴形成,并且促进肿瘤的增殖、提高肿瘤的侵袭性。
英文摘要:
      Objective: To investigate the mechanisms of IGFBP3 in the action on adjacent adipocytes and the effect of adjacent adipocytes on the proliferation and migration capability of clear cell renal cell carcinoma (ccRCC). Method(s): IGFBP3 was found to be overexpressed in the database of ccRCC, which was verified in the specimen of ccRCC. The effect of IGFBP3 on differentiation of adipocytes was detected from gene and protein level. Renal carcinoma cell line 786-O cell overexpressing IGFBP3 was used as cellular model and western blot was used to detect the effect of IGFBP3 on TGFβ pathway. Conditioned medium was prepared via cocultivation of 786-O overexpressing IGFBP3 and preadipocytes. Oil red staining was used to detect the contents of lipid droplets in renal carcinoma cell. Transwell and CCK8 was used to detect the effect of adipocytes on migration capability and proliferation of renal carcinoma cell. Result(s): The expression of IGFBP3 markedly increased in the specimen of renal cell carcinoma (P<0.05). IGFBP3 promoted the differentiation of preadipocyte after activating smad1/5/8 and p38MAPK (p<0.05). The contents of lipid droplets increased in 786-O cell cultivated in the conditioned medium and migration capability and proliferation of 786-O were promoted. Conclusion(s): IGFBP3, overexpressed in renal cell carcinoma, promoted the expression of preadipocyte by activating smad1/5/8 and p38MAPK. Mature adipocytes could increase the contents of lipid droplets and promoted migration capability and proliferation of renal cell carcinoma.
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