Innervation of cervical carcinoma is mediated by cancer-derived exosomes

Christopher T. Lucido, Emily Wynja, Marianna Madeo, Caitlin S. Williamson, Lauren E. Schwartz, Brittney A. Imblum, Ronny Drapkin, Paola D. Vermeer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalGynecologic Oncology
Volume154
Issue number1
DOIs
StatePublished - Jul 2019

Fingerprint

Exosomes
Uterine Cervical Neoplasms
Carcinoma
Neoplasms
PC12 Cells
Tubulin
Cell Line
Tumor Microenvironment
Neurites
Cervix Uteri
Staining and Labeling
Neuronal Outgrowth

Keywords

  • Cervical cancer
  • Exosomes
  • HPV
  • Innervation

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Lucido, C. T., Wynja, E., Madeo, M., Williamson, C. S., Schwartz, L. E., Imblum, B. A., ... Vermeer, P. D. (2019). Innervation of cervical carcinoma is mediated by cancer-derived exosomes. Gynecologic Oncology, 154(1), 228-235. https://doi.org/10.1016/j.ygyno.2019.04.651

Innervation of cervical carcinoma is mediated by cancer-derived exosomes. / Lucido, Christopher T.; Wynja, Emily; Madeo, Marianna; Williamson, Caitlin S.; Schwartz, Lauren E.; Imblum, Brittney A.; Drapkin, Ronny; Vermeer, Paola D.

In: Gynecologic Oncology, Vol. 154, No. 1, 07.2019, p. 228-235.

Research output: Contribution to journalArticle

Lucido, CT, Wynja, E, Madeo, M, Williamson, CS, Schwartz, LE, Imblum, BA, Drapkin, R & Vermeer, PD 2019, 'Innervation of cervical carcinoma is mediated by cancer-derived exosomes', Gynecologic Oncology, vol. 154, no. 1, pp. 228-235. https://doi.org/10.1016/j.ygyno.2019.04.651
Lucido CT, Wynja E, Madeo M, Williamson CS, Schwartz LE, Imblum BA et al. Innervation of cervical carcinoma is mediated by cancer-derived exosomes. Gynecologic Oncology. 2019 Jul;154(1):228-235. https://doi.org/10.1016/j.ygyno.2019.04.651
Lucido, Christopher T. ; Wynja, Emily ; Madeo, Marianna ; Williamson, Caitlin S. ; Schwartz, Lauren E. ; Imblum, Brittney A. ; Drapkin, Ronny ; Vermeer, Paola D. / Innervation of cervical carcinoma is mediated by cancer-derived exosomes. In: Gynecologic Oncology. 2019 ; Vol. 154, No. 1. pp. 228-235.
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