Society for Surgery of the Alimentary Tract
SSAT Home SSAT Home Past & Future Meetings Past & Future Meetings

Back to 2023 Abstracts

Richard Jacobson*1,2, John C. Alverdy2, Olga Zaborina2, Benjamin D. Shogan2
1Moffitt Cancer Center, Tampa, FL; 2University of Chicago Division of the Biological Sciences, Chicago, IL

Introduction: The urokinase-plasminogen system is a well-known promoter of colorectal cancer (CRC) progression. Its end-product, plasmin, mediates submucosal collagen degradation, chemotaxis, angiogenesis and growth factor release in the tumor microenvironment. We have previously demonstrated that selective gut pathogens, specifically, collagenase producing Enterococcus faecalis, that are known to overgrow during states of dysbiosis, can induce CRC invasion and migration in vitro and in vivo. In the present report we hypothesized that E. faecalis promotes increased plasmin production in cancer cells. Therefore the aim of this study was to demonstrate that co-incubation of CT26 colorectal cancer cells with collagenase producing E. faecalis increases their plasmin production.

Methods: 4 X 104 CT26 colorectal carcinoma cells and collagenolytic E. faecalis strain V583 were utilized for all experiments. After co-incubation of E. faecalis and CT26 cells, fluorescently labeled plasminogen (PLG) was added for two hours and PLG binding measured by fluorimetry after washing. Fluorogenic plasmin generation assays were used to measure the kinetics of PLG activation. Tranexamic acid (TXA), a small molecule, was used to inhibit PLG activation.

Results: Co-incubation of E. faecalis with CT 26 cells for 24 hours resulted in a significant increase in binding of PLG to CT26 cells compared to when E. faecalis was absent (Panel A - CT26 alone: 4.1+/-0.1*105 RFU vs CT26+EF 24hr 6.9+/-0.8*105 RFU, *p<0.05). This binding was not demonstrated during coincubation at 6 hours. The presence of E. faecalis resulted in a striking increase in active plasmin with a four-fold increase in activity at a multiplicity of infection (MOI) of 10 compared to when E. faecalis was absent (Panel B - CT26 alone: 1.7+/-0.1*104 RFU/s vs CT26+EF MOI 10: 6.8+/-0.1*104 RFU/s, *p<0.05) or at a MOI of 1. Tranexamic acid inhibited E.faecalis- induced PLG activation by CT26 cells in a concentration-dependent fashion (Panel C, *p<0.05).

Conclusions: E. faecalis induced cell surface binding of PLG to CT 26 cells and increased their activation of the growth-promoting enzyme plasmin. Given the central role of plasmin in cancer cell progression, further investigation into the role of bacterial-mediated PLG activation of CRC progression is warranted.

Back to 2023 Abstracts