Abstract
Abstract Colorectal cancer (CRC) is the third most diagnosed cancer and cause of cancer related mortality. CRC that metastasizes to distance sites results in poor prognosis, diminished survival, and reduced effectiveness of treatments. Perineural invasion (PNI) is an emerging field that aims to understand cancer-neuronal crosstalk that enables cancer to spread via nerves. Several studies have indicated that tumor derived exosomes (TDEs) play significant roles in the initiation and spread of cancer, along with driving chemoresistance. We hypothesize that CRC derived exosomes alter nerves within the surrounding environment and result in recruitment of nerves towards tumors for invasion along the nerve. Exosomes from both HCT116 and SW837 colon cancer cells were isolated and purified using a modified iodixanol ultracentrifugation gradient technique. A Proteomic analysis conducted on cancer derived exosomes revealed several potential proteins involved in neuronal growth and migration, including Vinculin (VCL), Periostin (POSTN or OSF-2), DCLK1, and USP9X. In another set of experiments, conditioned media (CM) from HCT116 and SW837 cells were added to both PC12 neuronal-like cells and dorsal root ganglion (DRG) from C57BL/6J mice to understand the effects of excreted cancer factors on neuronal outgrowth and differentiation. CM studies showed how signaling factors excreted from colon cancer cells induce increased nerite outgrowth in both PC12 cells and DRG. These results were not seen in CM from cancer cells that were grown in the presence of an exosome inhibitor. Altogether, these results indicate that CRC utilizes exosomes to alter the adjacent neuronal networks as a means to employ surrounding nerves for invasion. Citation Format: Colewyn Knoblich, Khosrow Rezvani. Released exosomes from colon cancer cells regulate formation and progression of perineural invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 261.
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