LAUSR

The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads of Fusobacterium nucleatum correlate with shorter survival in patients. Here, we investigated the potential mechanisms underlying this association. We found that F. nucleatum infection induced both normal pancreatic epithelial cells and PDAC cells to secrete increased amounts of the cytokines GM-CSF, CXCL1, IL-8, and MIP-3α. These cytokines increased proliferation, migration, and invasive cell motility in both infected and noninfected PDAC cells but not in noncancerous pancreatic epithelial cells, suggesting autocrine and paracrine signaling to PDAC cells. This phenomenon occurred in response to Fusobacterium infection regardless of the strain and in the absence of immune and other stromal cells. Blocking GM-CSF signaling markedly limited proliferative gains after infection. Thus, F. nucleatum infection in the pancreas elicits cytokine secretion from both normal and cancerous cells that promotes phenotypes in PDAC cells associated with tumor progression. The findings support the importance of exploring host-microbe interactions in pancreatic cancer to guide future therapeutic interventions. Description The host cell response to Fusobacterium infection promotes aggressive pancreatic cancer cell behavior. A tumorigenic infection The tumor-associated microbiome can contribute to tumor development and progression. Udayasuryan et al. found that Fusobacterium nucleatum—an oral commensal that can become an opportunistic pathogen—promotes tumor progression–associated activity in pancreatic ductal adenocarcinoma (PDAC) cells. Infection with various subspecies of F. nucleatum induced the release of cytokines that promoted proliferation, migration, and invasion in human PDAC cell lines but not in normal human pancreatic epithelial cells. Proliferation was prevented with an antibody that blocks one of the secreted cytokines, GM-CSF. The findings reveal a host-microbe interaction that may promote progression in PDAC and that may therefore inform clinical strategies for prognosis and therapeutic intervention.