Abstracto

Differential effects of lipoteichoic acid and lipopolysaccharides on gastric cancer cell proliferation via distinctive involvement of TLR2 signaling mediators.

Emily KY Lam, Emily KK Tai, William KK Wu, L Yu, Helen PS Wong, Vivian Y Shin, CH Cho

Toll like receptors (TLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns. TLR signaling activates the innate immune response and induces the adaptive immunity, suggesting its significance to be a target for anti-cancer immunotherapy. In this study, we show that lipoteichoic acid (LTA) derived from gram positive Streptococcus faecalis markedly inhibited AGS gastric cancer cell proliferation. This is likely attributed to the induction of TNF-α through the upregulation of TLR2 expression and its downstream mediators including cytosolic adapter molecule myeloid differentiation protein MyD88, TNF receptor-associated factor 6 (TRAF6) and NF-κB activation. Lipopolysaccharides (LPS) derived from gram-negative Escherichia coli, on the other hand, did not affect AGS cell proliferation and TNF-α expression. Interestingly, LPS also induced TLR2 and MyD88 protein expression without affecting the downstream TRAF6 expression and NF-κB activation. It is suggested that these microbial components derived from gram-positive and gram-negative bacteria elicited differential effects on gastric cancer cell proliferation. The ability of these microbial components to induce TRAF6 expression could be one of the crucial elements underlying its differential functional effects upon TLR2 induction.