Fusobacterium nucleatum induces pancreatic cancer cell proliferation and migration by regulating host autocrine and paracrine signaling

Abstract

Pancreatic ductal adenocarcinoma (PDAC) harbors a complex tumor microbiome that has been implicated in cancer progression and resistance to chemotherapy. Recent clinical investigations uncovered a correlation between high loads of intratumor Fusobacterium nucleatum and decreased patient survival. Here we show that pancreatic cancer cell lines harboring intracellular F. nucleatum secrete elevated levels of cancer-associated cytokines including IL-8, CXCL1, GM-CSF, and MIP-3α. We report that GM-CSF directly increases the proliferation of pancreatic cancer cells, and contributes to increased cellular migration, notably in the absence of immune cell participation. This study is the first to investigate the direct impact of F. nucleatum infection on pancreatic cancer cells. Our results suggest that F. nucleatum within the pancreatic tumor microenvironment elicits infection-specific cytokine secretion that directly contributes adversely to cancer progression and warrants further research into therapeutic manipulation of the pancreatic tumor microbiome.

Fusobacterium & Co. at the Stem of Cancer: Microbe–Cancer Stem Cell Interactions in Colorectal Carcinogenesis

“…Interestingly, advanced cancer tissue may become unhospitable to HP, thus justifying its disappearance [24,164] or substitution by other "passenger" bacteria, including F. nucleatum [165,166]. Conversely, F. nucleatum appears to be exceptionally well adapted to the cancerous environment, as confirmed by its emerging association with other non-CRC malignancies, such as pancreatic and breast cancer [27,[167][168][169].…”