Observing phenotypical changes conducive to perineural invasion in PCa cells via an NGF-rich, 3D hydrogel model
Date
2020
Authors
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Publisher
University of Delaware
Abstract
Prostate cancer (PCa) is the number one occurring carcinoma among men in the United States. An understudied, yet deadly clinical prognostication, route of PCa metastasis known as Perineural Invasion (PNI) entails cancer cells migrating along nerve bundles—using them as conduits to distal locations in the body. Current models of PNI involve the harvest and use of dorsal root ganglia (DRG), single cells, and a 3D matrix such as Matrigel. Issues with using such a model as this is that it fails to truly emulate the in vivo environment and cellular morphology observed in actual PNI. Most notably, many PCa types adopt a spheroid morphology and do not exist solely as single cells. ☐ The model proposed in the Jia lab wishes to make use of cultured PCa spheroids and a hyaluronic acid based hydrogel crosslinked via tetrazine ligation (HA-TZ gels). Essentially, PCa spheroids encapsulated in these HA gels along with neuromimetic fibers that will release a biochemical gradient of growth factor (such as nerve growth factor, NGF) and neurotransmitters. A model such as this ensures that cells are consistently in a 3D environment, and that they adopt a more realistic morphology. ☐ My studies showed that PC3 and DU145 cell lines were more aggressive and invasive than LNCap when cultured in Matrigel, HA-TZ gels, and Collagen I hydrogels. ☐ Induction of phenotypic changes within PCa cells, via NGF treatment, reminiscent of PNI remains uncertain. Under the 3D culture conditions employed in my study, NGF appears to induce cell migration, and alter the expression of epithelial markers in DU145 at the mRNA level. However, further investigation of epithelial and mesenchymal markers is required in order to determine if NGF treatment is activating signaling pathways which contribute towards a metastatic, partial-EMT phenotype in DU145.
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Keywords
Prostate cancer, Cellular morphology, Perineural invasion, Phenotypic changes