Global transcriptional response of oral squamous cell carcinoma cell lines to health-associated oral bacteria-an in vitro study

Background We have recently demonstrated that health-associated oral bacteria Streptococcus mitis, Neisseria flavescens, and Haemophilus parainfluenzae induce cytotoxicity in oral squamous cell carcinoma (OSCC) cell lines and downregulate CD36, a cancer-assocaited gene. Aim To explore the effect of these three species on global transcriptome of OSCC cell lines. Methods Gene expression of cell lines CAL27, SCC4 and SCC25 cocultured with the test species was assessed with Clariom-S Human microarray. Porphyromonas gingivalis was included as a pathogenic control. Data were analyzed using Ingenuity Pathway Analysis. Results The results differed by species and cell line. Overall, the transcriptional changes by S. mitis were predominantly anti-cancer including inhibition of HOTAIR regulatory pathway, JAK/Stat signaling, cyclins/cyclin-dependent kinases, and endothelin1 signaling. H. parainfluenzae and N. flavescens resulted in a mix of pro- and anti-cancer responses including activation of acute phase response, pro-inflammatory interleukins signaling, TREM-1 signaling, and tumor microenvironment pathway; but downregulation of cell cycle by inhibition of cyclins and cyclin-dependent kinases. P. gingivalis had a predominantly pro-cancer effect limited to SCC4, including upregulation of inflammatory pathways, phospholipases and PI3K signaling. Conclusion These findings provide a new insight into the role of commensal oral bacteria in OSCC. Animal studies are required to further explore them.

Automated summary

This study explores the role of health-associated oral bacteria in oral squamous cell carcinoma (OSCC) cell lines. The results show that different species of bacteria have varying effects on the cell lines, including inhibition of cancer-associated pathways, activation of acute phase response, and pro-inflammatory pathways. These findings provide a new understanding of oral cancer.