First, transcription factors NF-κB and STAT3 that regulate expression of inflammatory gene products, have been found to be constitutively active in most cancers; second, chronic inflammation such as pancreatitis, prostatitis, hepatitis etc. leads to cancers; third, activation of NF-κB and STAT3 leads to cancer cell proliferation, survival, invasion, angiogenesis and metastasis; fourth, activation of NF-κB and STAT3 leads to resistance to chemotherapy and radiation, and hypoxia and acidic conditions activate these transcription factors.
Using a Kras-driven mouse model of PDA, we establish that the inflammatory mediator Stat3 is a critical component of spontaneous and pancreatitis-accelerated PDA precursor formation and supports cell proliferation, metaplasia-associated inflammation, and MMP7 expression during neoplastic development.