title: Cancerous epithelial cell lines shed extracellular vesicles with a bimodal size distribution that is sensitive to glutamine inhibition.
abstract: Extracellular shed vesicles (ESVs) facilitate a unique mode of cell-cell communication wherein vesicle uptake can induce a change in the recipient cell's state. Despite the intensity of ESV research, currently reported data represent the bulk characterization of concentrated vesicle samples with little attention paid to heterogeneity. ESV populations likely represent diversity in mechanisms of formation, cargo and size. To better understand ESV subpopulations and the signaling cascades implicated in their formation, we characterize ESV size distributions to identify subpopulations in normal and cancerous epithelial cells. We have discovered that cancer cells exhibit bimodal ESV distributions, one small-diameter and another large-diameter population, suggesting that two mechanisms may govern ESV formation, an exosome population and a cancer-specific microvesicle population. Altered glutamine metabolism in cancer is thought to fuel cancer growth but may also support metastatic niche formation through microvesicle production. We describe the role of a glutaminase inhibitor, compound 968, in ESV production. We have discovered that inhibiting glutamine metabolism significantly impairs large-diameter microvesicle production in cancer cells.
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Steven Michael
authors.initials: SM
authors.lastname: Santana
authors.forename: Marc A
authors.initials: MA
authors.lastname: Antonyak
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cerione
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Kirby
mesh_terms: D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D055354:Exosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005110:Extracellular Space / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005972:Glutaminase / Q000032:analysis; D005973:Glutamine / Q000037:antagonists & inhibitors*; D006801:Humans; D022161:Transport Vesicles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005973:Glutamine; D005972:Glutaminase