@article{2f0651eed64e47fea5de70b94f02e2bb,
title = "Oral Cancer Cells Release Vesicles that Cause Pain",
abstract = "Oral cancer pain is attributed to the release from cancers of mediators that sensitize and activate sensory neurons. Intraplantar injection of conditioned media (CM) from human tongue cancer cell line HSC-3 or OSC-20 evokes nociceptive behavior. By contrast, CM from noncancer cell lines, DOK, and HaCaT are non-nociceptive. Pain mediators are carried by extracellular vesicles (EVs) released from cancer cells. Depletion of EVs from cancer cell line CM reverses mechanical allodynia and thermal hyperalgesia. CM from non-nociceptive cell lines become nociceptive when reconstituted with HSC-3 EVs. Two miRNAs (hsa-miR-21-5p and hsa-miR-221-3p) are identified that are present in increased abundance in EVs from HSC-3 and OSC-20 CM compared to HaCaT CM. The miRNA target genes suggest potential involvement in oral cancer pain of the toll like receptor 7 (TLR7) and 8 (TLR8) pathways, as well as signaling through interleukin 6 cytokine family signal transducer receptor (gp130, encoded by IL6ST) and colony stimulating factor receptor (G-CSFR, encoded by CSF3R), Janus kinase and signal transducer and activator of transcription 3 (JAK/STAT3). These studies confirm the recent discovery of the role of cancer EVs in pain and add to the repertoire of algesic and analgesic cancer pain mediators and pathways that contribute to oral cancer pain.",
keywords = "extracellular vesicles, miR-21, miR-221, miRNA, oral cancer, oral cancer induced pain, pain",
author = "Dubeykovskaya, {Zinaida A.} and Tu, {Nguyen Huu} and Garcia, {Paulina D.Ram{\'i}rez} and Schmidt, {Brian L.} and Albertson, {Donna G.}",
note = "Funding Information: Z.A.D. and N.H.T. contributed equally to this work, which was supported by NIH Grants R01CA228525 and R01CA231396. P.D.R.G. is the recipient of an International Association for the Study of Pain John J. Bonica Trainee Fellowship. The authors thank Kristen Dancel-Manning, NYU Langone Health Microscopy Laboratory for assistance with TEM work. The NanoString nCounter assays were performed by the NYU Langone Health Genome Technology Center. These shared resources are partially funded by the Laura and Isaac Perlmutter Comprehensive Cancer Center support grant, P30CA016087. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: Z.A.D. and N.H.T. contributed equally to this work, which was supported by NIH Grants R01CA228525 and R01CA231396. P.D.R.G. is the recipient of an International Association for the Study of Pain John J. Bonica Trainee Fellowship. The authors thank Kristen Dancel‐Manning, NYU Langone Health Microscopy Laboratory for assistance with TEM work. The NanoString nCounter assays were performed by the NYU Langone Health Genome Technology Center. These shared resources are partially funded by the Laura and Isaac Perlmutter Comprehensive Cancer Center support grant, P30CA016087. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2022 The Authors. Advanced Biology published by Wiley-VCH GmbH.",
year = "2022",
month = sep,
doi = "10.1002/adbi.202200073",
language = "English (US)",
journal = "Advanced Biology",
issn = "2701-0198",
publisher = "Wiley-VCH Verlag",
}