Journal
SCIENCE SIGNALING
Volume 15, Issue 756, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.abn4948
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Funding
- NIH R21 Exploratory/Developmental Research grant [1R21CA238630-01A1]
- NSF [CBET-1652112, ECCS 1542100, ECCS 2025151]
- Center for Engineered Health of the Institute for Critical Technology and Applied Sciences at Virginia Tech
- Biostatistics Shared Resource at the Wake Forest Comprehensive Cancer Center
- Virginia Tech National Center for Earth and Environmental Nanotechnology Infrastructure (NanoEarth)
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Infection with Fusobacterium can induce normal pancreatic epithelial cells and PDAC cells to secrete increased amounts of cytokines, promoting proliferation, migration, and invasive cell motility in PDAC cells. This phenomenon is associated with tumor progression.
The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pan-creatic 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 in-creased amounts of the cytokines GM-CSF, CXCL1, IL-8, and MIP-3 alpha. These cytokines increased proliferation, migration, and invasive cell motility in both infected and noninfected PDAC cells but not in noncancerous pan-creatic 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.
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