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Perineural Invasion, Colorectal Cancer, cancer


Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and is a leading cause of cancer related death worldwide. Cancer that migrates from the primary site to distant organs can create additional complications, which usually result in poor prognosis and reduced survival in patients. Perineural invasion (PNI) is an emerging field in cancer research that involves interactions between cancer and the nervous system as an alternative route for metastasis. The underlying mechanisms of cancer metastasis have been vastly studied, but the mechanisms of PNI are relatively understudied. We hypothesize that CRC induces formation of neurites, allowing for further interactions and cancer metastasis. Our work aims to better understand the mechanisms of PNI through in vitro studies in CRC patients. To test this, an in vitro coculture system containing both a PC12 neuronal cell line and a HCT116 human primary colon adenocarcinoma cell line were used to mimic the tumor microenvironment. Two types of cocultures were utilized. A contact coculture which investigates the effects of CRC that has invaded nerves, and transwell cocultures which identifies cross talk between the two types of cells via soluble factors/exosome secreted from cancer cells. The major focus of these cocultures is to identify if CRC is capable of inducing neurite growth and inhibit cell death (apoptosis) in PC12 cells. Our preliminary data indicates that incubation of PC12 cells with colon cancer cells, decreases the level of apoptosis following serum starvation. Additionally, the in vitro coculture system shows incubation of HCT116 with PC12 cells decreases late apoptosis and necrosis following serum starvation. Understanding the mechanism of PNI has a significant impact on blocking tumor progression and improving patient survival.

First Advisor

Khosrow Rezvani

Research Area

Basic Biomedical Sciences