Arsenic Alters Exosome Quantity and Cargo to Mediate Stem Cell Recruitment Into a Cancer Stem Cell-Like Phenotype

Toxicological Sciences : an Official Journal of the Society of Toxicology
Ntube N O NgalameErik J Tokar

Abstract

Inorganic arsenic is a human carcinogen that can target the prostate. Accumulating evidence suggests arsenic can disrupt stem cell (SC) dynamics during the carcinogenic process. Previous work demonstrated arsenic-transformed prostate epithelial (CAsE-PE) cells can recruit prostate SCs into rapidly acquiring a cancer SC (CSC) phenotype via the secretion of soluble factors. Exosomes are small, membrane-derived vesicles that contain lipids, RNA, and proteins, and actively contribute to cancer initiation and progression when taken up by target cells. Here we hypothesized that CAsE-PE cells are recruiting SCs to a CSC-like phenotype via exosomal signaling. CAsE-PE cells secreted 700% more exosomes than parental RWPE-1 cells. CAsE-PE exosomes were enriched with oncogenic factors, including oncogenes (KRAS, NRAS, VEFGA, MYB, and EGFR), inflammation-related (cyclooxygenase-2, interleukin 1B (IL1B), IL6, transforming growth factor-β, and tumor necrosis factor-A), and apoptosis-related (CASP7, CASP9, and BCL2) transcripts, and oncogenesis-associated microRNAs. When compared with SCs cultured in exosome-depleted conditioned medium (CM), SCs cultured in CM containing CAsE-PE-derived exosomes showed increased (198%) matrix metalloproteinase...Continue Reading

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Citations

Apr 23, 2020·Frontiers in Pharmacology·Batla S Al-SowayanBahauddeen M Alrfaei
Sep 15, 2019·Environmental Research·Alina-Andreea ZimtaIoana Berindan-Neagoe
Oct 27, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Caitlin G HoweCarrie V Breton
Dec 15, 2020·Metallomics : Integrated Biometal Science·Irene BarguillaAlba Hernández

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