Effects of Tumor-Associated E. coli Metabolites on Migration of Colorectal Cancer Cells

Abstract

Colorectal tumors have a close connection with the gut microbiome. Correlation between rearrangement in microbiome composition and disease progression has already been shown. However, the questions about the mechanisms underlying microorganisms and cancer cells interaction and the immediate effects of tumor-associated microbiomes on cancer cells remain open. In this work, we investigated the effects of metabolites of tumor-associated E.coli strains on the growth and migration of human colorectal cancer cell lines (HCT116, SW480 and HT29). Differences in the spectrum of synthesized organic acids from tumor-associated and probiotic M-17 strains were revealed. Specifically, tumor-associated E.coli produced more fumaric, malic and maleic acids, whereas the M-17 - more propionic, 2-oxobutyric and α-ketoglutaric acids. Upon exposure to metabolites from tumor-associated E.coli strains, HCT116 and SW480 cells showed an increased migration activity and HT29 cells - decreased migration activity in 2D and 3D culture models. Immunocytochemistry assay revealed decrease of E-cadherin in HCT116 and SW480 cells and FAK- in HT29, which explain different effects of E.coli metabolites on migratory capacity of colorectal cancer cells. Therefore, these results suggest that the effect of tumor-associated E.coli strains on cancer cells migration depends on their innate type of migration - single-cell or collective migration.