Gastrointestinal nematode-derived antigens alter colorectal cancer cell proliferation and migration through regulation of cell cycle and epithelial-mesenchymal transition proteins

Jacobs, Brittany-Amber, Prince, Sharon and Smith, Katherine Ann ORCID: https://orcid.org/0000-0001-8150-5702 2020. Gastrointestinal nematode-derived antigens alter colorectal cancer cell proliferation and migration through regulation of cell cycle and epithelial-mesenchymal transition proteins. International Journal of Molecular Sciences 21 (21) , 7845. 10.3390/ijms21217845

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Abstract

As the global incidences of colorectal cancer rises, there is a growing importance in understanding the interaction between external factors, such as common infections, on the initiation and progression of this disease. While certain helminth infections have been shown to alter the severity and risk of developing colitis-associated colorectal cancer, whether these parasites can directly affect colorectal cancer progression is unknown. Here, we made use of murine and human colorectal cancer cell lines to demonstrate that exposure to antigens derived from the gastrointestinal nematode Heligmosomoides polygyrus significantly reduced colorectal cancer cell proliferation in vitro. Using a range of approaches, we demonstrate that antigen-dependent reductions in cancer cell proliferation and viability are associated with increased expression of the critical cell cycle regulators p53 and p21. Interestingly, H. polygyrus-derived antigens significantly increased murine colorectal cancer cell migration, which was associated with an increased expression of the adherens junction protein β-catenin, whereas the opposite was true for human colorectal cancer cells. Together, these findings demonstrate that antigens derived from a gastrointestinal nematode can significantly alter colorectal cancer cell behavior. Further in-depth analysis may reveal novel candidates for targeting and treating late-stage cancer.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine Biosciences
Subjects:	Q Science > Q Science (General) R Medicine > R Medicine (General)
Publisher:	MDPI
ISSN:	1661-6596
Date of First Compliant Deposit:	26 October 2020
Date of Acceptance:	19 October 2020
Last Modified:	04 May 2023 14:17
URI:	https://orca.cardiff.ac.uk/id/eprint/135935

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