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

Colorectal tumors have a close connection with the gut microbiome.A correlation between rearrangement in microbiome composition and disease progression has already been shown. However, the mechanisms underlying interactions between microorganisms and cancer cells , as well as  the immediate effects of tumor-associated microbiomes on cancer cells, remain unclear. In this work, we investigated the effects of metabolites produced by tumor-associated E.coli strains on the migration of human colorectal cancer cell lines (HCT۱۱۶, SW۴۸۰ and HT۲۹). We identified differences in some biochemical enzime activity of E.coli strains and in the spectrum of synthesized organic acids between  tumor-associated strains and the probiotic E.coli M-۱۷ strains. Most strains associated with colorectal cancer were unable to utilize sucrose. Specifically, tumor-associated E.coli produced more fumaric, malic and maleic acids, whereas the E.coli M-۱۷ produced more short-chain fatty acids such as propionic, ۲-oxobutyric ,and α-ketoglutaric acids. Upon exposure to metabolites from tumor-associated E.coli strains, HCT۱۱۶ and SW۴۸۰ cells showed an increased migrationactivity , whereas HT۲۹ cells showed decreased migration activity in both ۲D and ۳D culture models. Immunocytochemistry assay revealed a decrease in E-cadherin in HCT۱۱۶ and SW۴۸۰ cells and FAK- in HT۲۹, which explains the 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 and enhances FAK-dependent single-cell migration accompanied by the loss of E-cadherin in cancer cells with initially low FAK expression. In contrast, this effect was not observed in cancer cells exhibiting a collective migration phenotype.

کلیدواژه ها:

Escherichia coli ، Metabolites ، colon cancer ، Migration