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Article

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma

1
Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St. North, Sioux Falls, SD 57104, USA
2
Sanford School of Medicine, University of South Dakota, 414 East Clark St., Vermillion, SD 57069, USA
3
Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd, Philadelphia, PA 19104, USA
4
Lincoln High School, 2900 South Cliff Avenue, Sioux Falls, SD 57105, USA
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Sanford Gynecologic Oncology, Sanford Health, 1309 West 17th St., Sioux Falls, SD 57104, USA
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Laboratory Medicine, Department of Pathology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Ilana Chefetz, Martina Bazzaro and Naweed I. Syed
Cells 2021, 10(12), 3491; https://doi.org/10.3390/cells10123491
Received: 1 September 2021 / Revised: 30 November 2021 / Accepted: 7 December 2021 / Published: 10 December 2021
(This article belongs to the Special Issue Ovary and Brain)
Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular–nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics. View Full-Text
Keywords: ovarian cancer; innervation; ultrasound; nerve-tracing ovarian cancer; innervation; ultrasound; nerve-tracing
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MDPI and ACS Style

Barr, J.L.; Kruse, A.; Restaino, A.C.; Tulina, N.; Stuckelberger, S.; Vermeer, S.J.; Williamson, C.S.; Vermeer, D.W.; Madeo, M.; Stamp, J.; Bell, M.; Morgan, M.; Yoon, J.-Y.; Mitchell, M.A.; Budina, A.; Omran, D.K.; Schwartz, L.E.; Drapkin, R.; Vermeer, P.D. Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma. Cells 2021, 10, 3491. https://doi.org/10.3390/cells10123491

AMA Style

Barr JL, Kruse A, Restaino AC, Tulina N, Stuckelberger S, Vermeer SJ, Williamson CS, Vermeer DW, Madeo M, Stamp J, Bell M, Morgan M, Yoon J-Y, Mitchell MA, Budina A, Omran DK, Schwartz LE, Drapkin R, Vermeer PD. Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma. Cells. 2021; 10(12):3491. https://doi.org/10.3390/cells10123491

Chicago/Turabian Style

Barr, Jeffrey L., Allison Kruse, Anthony C. Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J. Vermeer, Caitlin S. Williamson, Daniel W. Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A. Mitchell, Anna Budina, Dalia K. Omran, Lauren E. Schwartz, Ronny Drapkin, and Paola D. Vermeer. 2021. "Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma" Cells 10, no. 12: 3491. https://doi.org/10.3390/cells10123491

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