Abstract
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.
Original language | English (US) |
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Article number | 11150 |
Journal | Nature communications |
Volume | 7 |
DOIs | |
State | Published - Mar 29 2016 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy
MD Anderson CCSG core facilities
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- High Resolution Electron Microscopy Facility
- Research Animal Support Facility
- Small Animal Imaging Facility
- Cytogenetics and Cell Authentication Core
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Advanced Technology Genomics Core (ATGC)
Vicki D Huff (Director)
The University of Texas MD Anderson Cancer CenterEquipment/facility: Facility
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High Resolution Electron Microscopy Facility (HREMF)
Robert R. Langley (Director)
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