@article{9bc238d4f22340e1a7e660442ef785e7,
title = "Innervation of cervical carcinoma is mediated by cancer-derived exosomes",
abstract = "Objective: Recently, our laboratory identified sensory innervation within head and neck squamous cell carcinomas (HNSCCs) and subsequently defined a mechanism whereby HNSCCs promote their own innervation via the release of exosomes that stimulate neurite outgrowth. Interestingly, we noted that exosomes from human papillomavirus (HPV)-positive cell lines were more effective at promoting neurite outgrowth than those from HPV-negative cell lines. As nearly all cervical tumors are HPV-positive, we hypothesized that these findings would extend to cervical cancer. Methods: We use an in vitro assay with PC12 cells to quantify the axonogenic potential of cervical cancer exosomes. PC12 cells are treated with cancer-derived exosomes, stained with the pan-neuronal marker (β-III tubulin) and the number of neurites quantified. To assess innervation in cervical cancer, we immunohistochemically stained cervical cancer patient samples for β-III tubulin and TRPV1 (sensory marker) and compared the staining to normal cervix. Results: Here, we show the presence of sensory nerves within human cervical tumors. Additionally, we show that exosomes derived from HPV-positive cervical cancer cell lines effectively stimulate neurite outgrowth. Conclusions: These data identify sensory nerves as components of the cervical cancer microenvironment and suggest that tumor- derived exosomes promote their recruitment.",
keywords = "Cervical cancer, Exosomes, HPV, Innervation",
author = "Lucido, {Christopher T.} and Emily Wynja and Marianna Madeo and Williamson, {Caitlin S.} and Schwartz, {Lauren E.} and Imblum, {Brittney A.} and Ronny Drapkin and Vermeer, {Paola D.}",
note = "Funding Information: This work was supported by the National Institute of General Medical Sciences Center of Biomedical Research Excellence ( 5P20GM103548 ), the Sanford Research Molecular Pathology Core and Imaging Core ( 5P20GM103548 , P20GM103620 ); The Honorable Tina Brozman {"}Tina's Wish{"} Foundation ; The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation . Funding Information: This work was supported by the National Institute of General Medical Sciences Center of Biomedical Research Excellence (5P20GM103548), the Sanford Research Molecular Pathology Core and Imaging Core (5P20GM103548, P20GM103620); The Honorable Tina Brozman “Tina's Wish” Foundation; The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. RD serves on the scientific advisory boards of Siamab Therapeutics, Inc. and Repare Therapeutics, Inc. PDV has a patent pending on a novel therapeutic for tumor control and a licensing agreement with NantHealth for an HPV vaccine. Christopher T. Lucido: generation of hypothesis, purification of exosomes, PC12 assay and quantification, scoring of IHC staining, writing of manuscipt. Emily Wynja: writing of introduction, scoring of IHC staining, review of manuscript. Marianna Madeo: scoring of IHC staining, validation of PC12 assay quantification, review of manuscript. Caitlin S. Williamson: procurement of human samples, review of manuscript. Lauren E. Schwartz: procurement of human samples, review of manuscript. Brittney A. Imblum: procurement of additional human samples, review of manuscript. Ronny Drapkin: generation of hypothesis, procurement of human samples, review of manuscript. Paola D. Vermeer: generation of hypothesis, writing of manuscript, analysis of all data. All authors have approved the final article. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = jul,
doi = "10.1016/j.ygyno.2019.04.651",
language = "English (US)",
volume = "154",
pages = "228--235",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "1",
}