Stromal cell extracellular vesicular cargo mediated regulation of breast cancer cell metastasis via ubiquitin conjugating enzyme E2 N pathway
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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
Radhika Pochampally, email: firstname.lastname@example.org
Keywords: exosomes; dormancy; MSCs; miRNA; signalling
Received: April 15, 2017 Accepted: October 13, 2017 Published: November 10, 2017
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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