Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1

被引：636

作者：

Yeung, Chi Lam Au ^{[1
]}

Co, Ngai-Na ^{[1
]}

Tsuruga, Tetsushi ^{[1
]}

Yeung, Tsz-Lun ^{[1
]}

Kwan, Suet-Ying ^{[1
]}

Leung, Cecilia S. ^{[1
]}

Li, Yong ^{[2
]}

Lu, Edward S. ^{[1
]}

Kwan, Kenny ^{[1
]}

Wong, Kwong-Kwok ^{[1
]}

Schmandt, Rosemarie ^{[1
]}

Lu, Karen H. ^{[1
]}

Mok, Samuel C. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, 1515 Holcombe Blvd,Unit 1362, Houston, TX 77030 USA

[2] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

美国国家卫生研究院;

关键词：

PROSTATE-CANCER; MESSENGER-RNAS; TUMOR; EXPRESSION; MICRORNAS; ACTIVATION; MICROVESICLES; FIBROBLASTS; PROGRESSION; APOPTOSOME;

D O I：

10.1038/ncomms11150

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer.

引用

页数：14

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