Since acquisition of Gem‑R increased IL‑8 production and consequently increased tumor angiogenesis, the IL‑8/CXCR2 axis may be a potential novel therapeutic target for PaCa after acquiring Gem‑R.
Of the factors identified, interleukin-8 (IL-8) is released at high levels from PC cells and PC/TAS co-culture and has previously been associated with low muscle mass in cancer patients.
Nested case-control studies examining the association between serum markers of chronic inflammation, focused on three specific biomarkers (CRP, IL-8 and TNF-α), and risk of pancreatic cancer have reported no associations.
Gene expression analysis in PDAC tumors (n = 63) showed a positive correlation between the expression of NOS2 and the tryptophan/kynurenine pathway genes, including indoleamine-2,3-dioxygenase 1 (IDO1) and several aryl hydrocarbon receptor (AHR)-target genes including NFE2L2 (NRF2), SERPINB2, IL1b, IL6 and IL8, which are implicated in pancreatic cancer.
IFN-γ treatment decreased the expression and secretion of CXCL8 in BxPC-3 PC cells, suppressed the proliferation and migration of these cells, and enhanced their apoptosis, as determined by increased levels of cleaved Caspase-8 and Bax together with reduced expression of Bcl-2.
Our studies suggest that IL-8 might be a malignant factor in human pancreatic cancer by induction of vascular endothelial growth factor and NRP-2 expression and ERK activation.
Collectively, our data demonstrated that constitutive NF-kappaB and AP-1 activation contributes to the overexpression of IL-8, which in turn plays an important role in tumor angiogenesis and contributes to the aggressive biology of human pancreatic cancer.
To directly determine the role of IL-8 in the growth and metastasis of pancreatic cancer, FG cells were transfected with IL-8 sense or antisense oligonucleotide expression vectors.
These data suggest that hypoxic environments upregulate the IL-8 gene via cooperation of NF-kappaB and AP-1 and contribute to the progression and metastasis of human pancreatic cancer.