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 journalArticlepeer-review

31 Scopus citations


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
Issue number1
StatePublished - Jul 2019


  • Cervical cancer
  • Exosomes
  • HPV
  • Innervation

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology


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