Oncotarget

Research Papers:

Stromal cell extracellular vesicular cargo mediated regulation of breast cancer cell metastasis via ubiquitin conjugating enzyme E2 N pathway

Krishna C. Vallabhaneni, Patrice Penfornis, Fei Xing, Yoni Hassler, Kristen V. Adams, Yin-Yuan Mo, Kounosuke Watabe and Radhika Pochampally _

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Oncotarget. 2017; 8:109861-109876. https://doi.org/10.18632/oncotarget.22371

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Abstract

Krishna C. Vallabhaneni1,2, Patrice Penfornis1, Fei Xing3, Yoni Hassler1, Kristen V. Adams4, Yin-Yuan Mo1, Kounosuke Watabe3,5 and Radhika Pochampally1,6

1Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA

2Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39216, USA

3Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

4Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA

5Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

6Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS 39216, USA

Correspondence to:

Radhika Pochampally, email: rpochampally@umc.edu

Keywords: exosomes; dormancy; MSCs; miRNA; signalling

Received: April 15, 2017     Accepted: October 13, 2017     Published: November 10, 2017

ABSTRACT

Mesenchymal stromal cells (hMSCs) have been used to understand the stromal cell properties in solid tumors because of their ablity to differentiate into most cell types. We investigated the role of EVs from hMSCs (hMSC-EVs) in breast cancer metastasis using MDA-MB-231 parental cell line and organotropic sub-lines. We demonstrated that hMSC-EVs significantly suppressed the metastatic potential of the parental cell line when compared to their organotropic sublines. hMSC-EVs induce dormancy in the parental cell line but not in their organotropic sub-lines and miR-205 and miR-31 from EV cargo played a role. Further, Ubiquitin Conjugating Enzyme E2 N (UBE2N/Ubc13) - metastasis-regulating gene, is a target of these miRNAs and silencing of UBE2N/Ubc13 expression significantly suppressed migration, invasion, and proliferation of breast cancer cells. To summarize, hMSC-EVs support primary breast tumor progression but suppress the metastasis of breast cancer cells that are not organ-committed through the UBE2N/Ubc13 pathway and play a role in premetastic niche formation.


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