PMID- 36555753 OWN - NLM STAT- MEDLINE DCOM- 20221226 LR - 20230317 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 24 DP - 2022 Dec 17 TI - Extracellular Vesicles as Mediators of Nickel-Induced Cancer Progression. LID - 10.3390/ijms232416111 [doi] LID - 16111 AB - Emerging evidence suggests that extracellular vesicles (EVs), which represent a crucial mode of intercellular communication, play important roles in cancer progression by transferring oncogenic materials. Nickel (Ni) has been identified as a human group I carcinogen; however, the underlying mechanisms governing Ni-induced carcinogenesis are still being elucidated. Here, we present data demonstrating that Ni exposure generates EVs that contribute to Ni-mediated carcinogenesis and cancer progression. Human bronchial epithelial (BEAS-2B) cells and human embryonic kidney-293 (HEK293) cells were chronically exposed to Ni to generate Ni-treated cells (Ni-6W), Ni-transformed BEAS-2B cells (Ni-3) and Ni-transformed HEK293 cells (HNi-4). The signatures of EVs isolated from Ni-6W, Ni-3, HNi-4, BEAS-2B, and HEK293 were analyzed. Compared to their respective untreated cells, Ni-6W, Ni-3, and HNi-4 released more EVs. This change in EV release coincided with increased transcription of the EV biogenesis markers CD82, CD63, and flotillin-1 (FLOT). Additionally, EVs from Ni-transformed cells had enriched protein and RNA, a phenotype also observed in other studies characterizing EVs from cancer cells. Interestingly, both epithelial cells and human umbilical vein endothelial (HUVEC) cells showed a preference for taking up Ni-altered EVs compared to EVs released from the untreated cells. Moreover, these Ni-altered EVs induced inflammatory responses in both epithelial and endothelial cells and increased the expression of coagulation markers in endothelial cells. Prolonged treatment of Ni-alerted EVs for two weeks induced the epithelial-to-mesenchymal transition (EMT) in BEAS-2B cells. This study is the first to characterize the effect of Ni on EVs and suggests the potential role of EVs in Ni-induced cancer progression. FAU - Liu, Shan AU - Liu S AUID- ORCID: 0000-0003-0012-7282 AD - Division of Environmental Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Ortiz, Angelica AU - Ortiz A AUID- ORCID: 0000-0003-4008-7203 AD - Division of Environmental Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Stavrou, Aikaterini AU - Stavrou A AUID- ORCID: 0000-0001-7922-6691 AD - Division of Environmental Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Talusan, Angela R AU - Talusan AR AUID- ORCID: 0000-0002-3543-2132 AD - Division of Environmental Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Costa, Max AU - Costa M AD - Division of Environmental Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10010, USA. LA - eng GR - R01 ES030572/ES/NIEHS NIH HHS/United States GR - R01 ES030583/ES/NIEHS NIH HHS/United States GR - R01 CA217923/CA/NCI NIH HHS/United States GR - CA229234-02/NH/NIH HHS/United States GR - CA217923-03/NH/NIH HHS/United States GR - ES030572-02/NH/NIH HHS/United States GR - ES029359-03/NH/NIH HHS/United States GR - ES030583-02/NH/NIH HHS/United States GR - R01 CA229234/CA/NCI NIH HHS/United States GR - R01 ES029359/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20221217 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 7OV03QG267 (Nickel) SB - IM MH - Humans MH - Nickel/toxicity/metabolism MH - HEK293 Cells MH - *Neoplasms/metabolism MH - Human Umbilical Vein Endothelial Cells/metabolism MH - *Extracellular Vesicles/metabolism MH - Carcinogenesis/metabolism PMC - PMC9785150 OTO - NOTNLM OT - cancer OT - extracellular vesicles OT - nickel COIS- The authors declare no conflict of interest. EDAT- 2022/12/24 06:00 MHDA- 2022/12/27 06:00 PMCR- 2022/12/17 CRDT- 2022/12/23 01:36 PHST- 2022/11/08 00:00 [received] PHST- 2022/12/07 00:00 [revised] PHST- 2022/12/13 00:00 [accepted] PHST- 2022/12/23 01:36 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/27 06:00 [medline] PHST- 2022/12/17 00:00 [pmc-release] AID - ijms232416111 [pii] AID - ijms-23-16111 [pii] AID - 10.3390/ijms232416111 [doi] PST - epublish SO - Int J Mol Sci. 2022 Dec 17;23(24):16111. doi: 10.3390/ijms232416111.