Uncovering the effects of lipopolysaccharides from Porphyromonas gingivalis in the promotion of brain tumor proliferation 9344

Abstract Description Astrocytes, key glial cells, support Central Nervous System homeostasis and the blood-brain barrier (BBB) but can become reactive under inflammatory stimuli, potentially promoting tumor development. The mechanisms driving astrocyte transformation into astrocytoma remain unclear. Lipopolysaccharides (LPS) from Porphyromonas gingivalis (Pg), an oral pathogen, are capable of crossing the BBB and inducing inflammation. We hypothesize that Pg-LPS stimulates astrocyte reactivity and glioma-like proliferation. Using a dose-response curve, human primary astrocytes and iPSC-derived cortical brain organoids were treated with Pg-LPS [1 μg/mL] for 24 hours, followed by assessment of oncogenic markers (Ki67, COX-2) via western blot. Pg-LPS significantly increased astrocyte viability (p = 0.025) without altering Ki67 expression in astrocytes, compared to untreated. However, it showed slight Ki67 increases in organoids. Conversely, LPS from E. coli had no effect, and lipoteichoic acid from S. aureus reduced Ki67 by over 50%. Pg-LPS may enhance proliferation in brain organoids, composed of neurons, oligodendrocytes, and astrocytes. Future studies will identify the specific proliferative cell type and the roles of toll-like receptors 2 and 4. These findings may advance understanding of inflammatory mechanisms involved in glioma proliferation. Funding Sources NIHMHD U54 MD007600, NINDS K22NS118975, 5R21NS131061-02, NIGMS PR-INBRE 5P20GM103475, The Alliance U54GM133807, HiREC S21MD001830, and Título V RCM PO31S200104. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)