Gastrointestinal Nematode-Derived Antigens Alter Colorectal Cancer Cell Proliferation and Migration through Regulation of Cell Cycle and Epithelial-Mesenchymal Transition Proteins

Int J Mol Sci. 2020 Oct 22;21(21):7845. doi: 10.3390/ijms21217845.

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.

Keywords: colorectal cancer; gastrointestinal nematode; migration; proliferation.

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Antigens, Helminth / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / physiology
  • HCT116 Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Nematospiroides dubius / immunology*
  • Nematospiroides dubius / metabolism
  • Schistosoma mansoni / immunology
  • Schistosomiasis mansoni / immunology
  • Species Specificity
  • Tumor Suppressor Protein p53 / metabolism
  • beta Catenin / metabolism

Substances

  • Antigens, Helminth
  • CTNNB1 protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin