Fusobacterium nucleatum subsp. polymorphum induces invasive growth and angiogenic responses in malignant oral keratinocytes that are cell line- and bacterial strain-specific

Fusobacterium nucleatum is an anaerobic commensal of the oral cavity recently associated cancers of the gastrointestinal tract, including oral squamous cell carcinoma (OSCC). In this study, we investigate the impact on oral keratinocytes of infection with a clinically relevant and genetically diverse set of strains of F. nucleatum subsp. polymorphum recovered from patients with oral dysplasia (n=6). We employed an E-cadherin positive cell line derived from a grade 1 tumour (H357) and an and E-cadherin negative, Gal-GalNac expressing cell line derived from a grade 3 tumour (H376). Cellular invasion of the E-cadherin positive cells was associated with specific transcriptional responses including autophagy and keratinization. Infection of both H357 and H376 cell lines induced transcriptional and cytokine responses linked to cancer cell migration and angiogenesis. Our data indicate that the outcomes of F. nucleatum-oral cell interactions can vary greatly depending on the bacterial genotype and the malignant phenotype of the host cell.