title: Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites.
abstract: Human mesenchymal stem/stromal cells (hMSCs) have been shown to support breast cancer cell proliferation and metastasis, partly through their secretome. hMSCs have a remarkable ability to survive for long periods under stress, and their secretome is tumor supportive. In this study, we have characterized the cargo of extracellular vesicular (EV) fraction (that is in the size range of 40-150nm) of serum deprived hMSCs (SD-MSCs). Next Generation Sequencing assays were used to identify small RNA secreted in the EVs, which indicated presence of tumor supportive miRNA. Further assays demonstrated the role of miRNA-21 and 34a as tumor supportive miRNAs. Next, proteomic assays revealed the presence of ≈150 different proteins, most of which are known tumor supportive factors such as PDGFR-β, TIMP-1, and TIMP-2. Lipidomic assays verified presence of bioactive lipids such as sphingomyelin. Furthermore, metabolite assays identified the presence of lactic acid and glutamic acid in EVs. The co-injection xenograft assays using MCF-7 breast cancer cells demonstrated the tumor supportive function of these EVs. To our knowledge this is the first comprehensive -omics based study that characterized the complex cargo of extracellular vesicles secreted by hMSCs and their role in supporting breast cancers.
authors: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Krishna C
authors: KC
authors: Vallabhaneni
authors: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Patrice
authors: P
authors: Penfornis
authors: Department of Chemical and Biomolecular Engineering, New Orleans, LA, USA.
authors: Santosh
authors: S
authors: Dhule
authors: 3P5 Proteomic Platform of the Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Francois
authors: F
authors: Guillonneau
authors: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Kristen V
authors: KV
authors: Adams
authors: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Yin Yuan
authors: YY
authors: Mo
authors: Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, USA.
authors: Rui
authors: R
authors: Xu
authors: Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, USA.
authors: Yiming
authors: Y
authors: Liu
authors: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Kounosuke
authors: K
authors: Watabe
authors: Stem Cell Biology, Thermo Fisher Scientific, Frederick, MD, USA.
authors: Mohan C
authors: MC
authors: Vemuri
authors: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Radhika
authors: R
authors: Pochampally
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000473:pathology; D005260:Female; D064593:Heterografts; D006801:Humans; D050356:Lipid Metabolism; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs; D020543:Proteome
keywords: breast cancer; exosomes; mesenchymal stem cells; microRNA; tumor microenvironment