Porphyromonas somerae Invasion of Endometrial Cancer Cells

Abstract

Recent evidence suggests an association between endometrial cancer and the understudied bacterial species <i>Porphyromonas somerae</i>. This association was demonstrated in previous work that indicated a significantly enriched abundance of <i>P. somerae</i> in the uterine microbiome of endometrial cancer patients. Given the known associations of the <i>Porphyromonas</i> genus and oral cancer, we hypothesized that <i>P. somerae</i> may play a similar pathogenic role in endometrial cancer via intracellular activity. Before testing our hypothesis, we first characterized <i>P. somerae</i> biology, as current background data is limited. These novel characterizations include growth curves in liquid medium and susceptibility tests to antibiotics. We tested our hypothesis by examining growth changes in response to 17β-estradiol, a known risk factor for endometrial cancer, followed by metabolomic profiling in the presence and absence of 17β-estradiol. We found that <i>P. somerae</i> exhibits increased growth in the presence of 17β-estradiol of various concentrations. However, we did not find significant changes in metabolite levels in response to 17β-estradiol. To study direct host-microbe interactions, we used <i>in vitro</i> invasion assays under hypoxic conditions and found evidence for intracellular invasion of <i>P. somerae</i> in endometrial adenocarcinoma cells. We also examined these interactions in the presence of 17β-estradiol but did not observe changes in invasion frequency. Invasion was shown using three lines of evidence including visualization via differential staining and brightfield microscopy, increased frequency of bacterial recovery after co-culturing, and <i>in silico</i> methods to detail relevant genomic and transcriptomic components. These results underscore potential intracellular phenotypes of <i>P. somerae</i> within the uterine microbiome. Furthermore, these results raise new questions pertaining to the role of <i>P. somerae</i> in the progression of endometrial cancer.