雌激素
细胞生长
癌症研究
癌相关成纤维细胞
生物
MMP2型
免疫印迹
癌细胞
细胞
癌症
细胞迁移
分子生物学
内分泌学
转移
生物化学
遗传学
基因
作者
Shouxin Zhang,Xiliang Cong,Zhiguo Li,Yingwei Xue
标识
DOI:10.1016/j.intimp.2019.105937
摘要
As a common disease, gastric cancer (GC) has influenced over 1 million people worldwide. Despite of prevention and optimal treatments, GC still has a high mortality. The role of cancer-associated fibroblasts (CAFs) in tumor progression has recently attracted attention, yet few studies have focused on GC. Estrogen has been reported to relate to the poor prognosis of GC. Therefore, we investigated whether estrogen can stimulate CAFs to produce tumor promoting factors in this study. Gastric CAFs were isolated from GC tissues and treated with estrogen. ELISA results suggested that CAFs produced interleukin-6 (IL-6) after estrogen treatment in a dose-dependent manner. The cell culture supernatant for estrogen-treated CAFs was collected and used as conditioned medium (CM) for GC cells. After cultured in CM, increased cell proliferation and alteration of cell cycle were detected by CCK-8 assay, BrdU assay, and flow cytometry. Western blot and gelatin zymography were used to determine cancer invasion-associated proteins. Results indicated that the expression of matrix metalloproteinase 2 (MMP2) and MMP9 were enhanced by Estrogen-CAFs-CM. Additional transwell assay showed that cell invasion and migration were promoted after cultured in CM. Lastly, western blot and immunofluorescence results demonstrated that the level of phosphorylated signal transducer and activator of transcription 3 (STAT3) in GC cells increased after cultured in CM. The effect was neutralized by IL-6 neutralizing antibody and STAT3 siRNA. Conclusively speaking, estrogen can activate CAFs to produce IL-6, ending up with promotion of GC cell proliferation and invasion. This result may suggest a new therapeutic target for GC.
科研通智能强力驱动
Strongly Powered by AbleSci AI