Document Type
Thesis
Date of Award
2024
Degree Name
Master of Science (MS)
Department
Basic Biomedical Science
First Advisor
Kurt Warnhoff, Paola Vermeer
Abstract
It is now widely accepted that peripheral solid tumors are infiltrated by nerves. This infiltration of malignancies by nerves is referred to as tumor innervation. The Vermeer laboratory studies tumor innervation primarily in head and neck squamous cell carcinoma using a syngeneic cell line representing a mutationally-induced form of the disease; these cells are called MOC2-7 cells. In addition to defining the molecular consequences of tumor-infiltrating nerves on disease, the lab also focuses on their influence on behavior. This is important as cancer patients have a significantly higher incidence of depression and anxiety as compared to the population at large. In humans, males are more susceptible to head and neck cancers than females, thus few studies have analyzed this disease using female animals. To assess the impact of tumor-infiltrating nerves on disease, MOC2-7 cells were orthotopically implanted into the mouse oral cavity and tumor growth, innervation, and cancer-associated behavioral changes in female mice were characterized and compared to their male counterparts. We found that MOC2-7 tumors grow significantly slower in females. Surprisingly, tumors were also significantly more innervated in females. However, there were no differences in behavioral decline between tumor-bearing males and females. These findings suggest that nerve recruitment may differ between males and females. Treatment of tumors with cisplatin and radiation, standard-of-care treatment for HNSCC patients, slowed tumor growth for both male and female mice. Interestingly, tumors from treated mice were also significantly more innervated compared to untreated mice, with females having a greater increase in nerve density. Moreover, treatment did not appear to improve tumor-associated behavior changes. The tumor-brain circuit did not differ between males and females, regardless of treatment, indicating that the observed changes of increased innervation only had a local impact on the tumor. Head and neck cancer patients often receive the same treatment regardless of sex. From our studies, it is clear that sex has an influence on tumor growth and innervation, and that treatment may exacerbate tumor innervation. Thus, it is important that we, as a field, continue to study this disease in the female population.
Subject Categories
Neuroscience and Neurobiology
Keywords
Cancer, Cancer neuroscience, Head and neck cancer, Head and Neck Squamous Cell Carcinoma, HPV negative HNSCC, Tumor innervation
Number of Pages
35
Publisher
University of South Dakota
Recommended Citation
Barclay, Sarah, "CHARACTERIZING SEX DIFFERENCES IN HPV NEGATIVE HEAD AND NECK SQUAMOUS CELL CARCINOMA" (2024). Dissertations and Theses. 239.
https://red.library.usd.edu/diss-thesis/239