Stroma-derived extracellular vesicles deliver tumor-suppressive miRNAs to pancreatic cancer cells

Oncotarget
Song HanSteven J Hughes

Abstract

The biology of tumor-associated stroma (TAS) in pancreatic ductal adenocarcinoma (PDAC) is not well understood. The paradoxical observation that stroma-depletion strategies lead to progression of PDAC reinforced the need to critically evaluate the functional contribution of TAS in the initiation and progression of PDAC. PDAC and TAS cells are unique in their expression of specific miRNAs, and this specific miRNA expression pattern alters host to tumor microenvironment interactions. Using primary human pancreatic TAS cells and primary xenograft PDAC cells co-culture, we provide evidence of miRNA trafficking and exchanging between TAS and PDAC cells, in a two-way, cell-contact independent fashion, via extracellular vesicles (EVs) transportation. Selective packaging of miRNAs into EVs led to enrichment of stromal specific miR-145 in EVs secreted by TAS cells. Exosomes, but not microvesicles, derived from human TAS cells demonstrated a tumor suppressive role by inducing PDAC cell apoptosis. This effect was mitigated by anti-miR-145 sequences. Our data suggest that TAS-derived miRNAs are delivered to adjacent PDAC cells via exosomes and suppress tumor cell growth. These data highlight that TAS cells secrete exosomes carrying tumor s...Continue Reading

References

Jan 30, 2008·Current Protocols in Cell Biology·Clotilde ThéryAled Clayton
Feb 4, 2010·Cancer Research·Yiwei LiFazlul H Sarkar
Nov 26, 2010·Cancer Research·Jason WebberAled Clayton
Jan 21, 2012·Trends in Cell Biology·Xi ChenChen-Yu Zhang
Nov 14, 2013·Journal of Extracellular Vesicles·Rossella CrescitelliJan Lötvall
Jan 1, 2014·OncoTargets and Therapy·Albrecht NeessePatrick Michl
Jun 26, 2014·BioMed Research International·Catarina Roma-RodriguesPedro Viana Baptista
Aug 6, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Roy van der MeelRaymond M Schiffelers
Aug 16, 2014·Journal of Cellular and Molecular Medicine·Shi-Yun CuiLong-Bang Chen
Jan 7, 2015·International Journal of Cancer. Journal International Du Cancer·Patrice PenfornisRadhika Pochampally
Apr 29, 2015·Methods : a Companion to Methods in Enzymology·Maureen F PetersonTravis J Antes
May 23, 2015·Gut·Albrecht NeesseThomas M Gress
Sep 1, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Song HanSteven J Hughes
Nov 17, 2015·Cancer Letters·Srinivasa P PothulaMinoti V Apte
Nov 26, 2015·Oncotarget·Ci-Xiang ZhouQian Zhao
Jan 6, 2016·Nature Reviews. Rheumatology·Jos MaldaMarca H M Wauben
Feb 6, 2016·Experimental Hematology & Oncology·Amanda J FavreauPradeep Sathyanarayana
Feb 11, 2016·International Journal of Molecular Sciences·Shin-Ichiro OhnoMasahiko Kuroda
Oct 31, 2016·Advanced Drug Delivery Reviews·Pieter VaderRaymond M Schiffelers
Aug 11, 2016·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Saini SetuaSubhash C Chauhan
Sep 17, 2016·Genes & Development·Xin LiuMichael C Ostrowski
Nov 20, 2016·Journal of Extracellular Vesicles·Reka A HarasztiAnastasia Khvorova
Jan 24, 2017·International Journal of Oncology·Xi ZhouZhao Duan
Feb 25, 2017·The Journal of Experimental Medicine·Daniel ÖhlundDavid A Tuveson

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Citations

Sep 7, 2019·International Journal of Molecular Sciences·Bin LanChristian Pilarsky
Apr 4, 2021·Biomedicines·Laura De LellisSerena Veschi
Apr 30, 2021·Frontiers in Cell and Developmental Biology·Qi ChenXiaolan Zhu
Sep 10, 2021·Journal of Hematology & Oncology·Moritz Reese, Sameer A Dhayat

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Methods Mentioned

BETA
transfection
PCR
transfections
transmission electron microscopy
Flow
flow cytometry
xenograft
fluorescence microscopy

Software Mentioned

Evos
Nanoparticle tracking analysis ( NTA )
Prism

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