RRC ID 82715
Author Sasaki Y, Sato Y, Nomura K, Wakita A, Nagaki Y, Sasamori R, Yoneya T, Takahashi T, Yamada M, Takahashi M, Terata K, Imai K.
Title Peptidoglycan induces CXCL10 production and inhibits esophageal squamous cell carcinoma proliferation.
Journal Am J Cancer Res
Abstract Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC); thus, good oral health may reduce the risk of ESCC. We previously reported that high expression of Toll-like receptor (TLR) 6, which recognizes peptidoglycan (PGN) from Gram-positive bacteria correlates with a good prognosis after esophagectomy for ESCC. Most beneficial bacteria in the mouth are Gram-positive. We therefore hypothesized that PGN affects cancer cell proliferation and disease progression in ESCC. To test that idea, we assessed the expression of cytokine and chemokine mRNA and protein in eight ESCC cell lines. We also employed a mouse xenograft model to investigate the effect of PGN on ESCC tumor progression in vivo. We then investigated the relationship between the combined expression profiles of TLR6 and C-X-C motif chemokine ligand 10 (CXCL10) in clinical samples and 5-year overall survival (OS) and disease-specific survival (DSS) in ESCC patients after curative esophagectomy. We found that PGN significantly inhibited cell proliferation in six of eight ESCC lines and upregulated CXCL10 production via NF-κB2. In vivo, subcutaneous PGN administration tended to decrease ESCC tumor volume in mice. Combined high expression of TLR6 and CXCL10 correlated with a better prognosis in ESCC patients. This suggests that PGN reduces cell proliferation and tumor progression through a PGN-TLR-CXCL10 cascade, thereby influencing prognosis after esophagectomy for ESCC, and that improving the oral environment could potentially improve the prognosis of ESCC patients after esophagectomy.
Volume 14(12)
Pages 5874-5884
Published 2024-1-1
DOI 10.62347/NHPV3701
PMID 39803645
PMC PMC11711533
Resource
Human and Animal Cells TE-8(RCB2098) TE-10(RCB2099)