Article: Santana SM, Antonyak MA, Cerione RA, Kirby BJ (2014) “Cancerous Epithelial Cell Lines Shed Extracellular Vesicles with a Bimodal Size Distribution That is Sensitive to Glutamine Inhibition”, Physical Biology, 11(6)
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.
Funding Acknowledgement: National Cancer Institutes [U54CA143876]; National Science Foundation GK-12 Program ; Alfred P. Sloan Foundation.
Funding Text: This work was supported by the National Cancer Institutes under Award Number U54CA143876, the National Science Foundation GK-12 Program under Award Number 0841291 and the Alfred P. Sloan Foundation. hTERT-HPNE cells were provided by National Institutes of Health Physical Sciences in the Oncology Network Bioresource Core Facility.