CXCR4 (CXCL12) expression levels were higher in pancreatic cancer 56.7% (86.7%), paracancerous tissue 50.0% (85.0%) and surrounding lymph nodes 53.3% (80.0%), compared with in normal tissues 18.3% (45.0%).
The present study indicated that Artemin induced CXCR4 expression by activating Akt and ERK 1/2/NF-κB signaling, thereby modulating tumor cell metastatic potential and invasion activity in pancreatic cancer by regulating SDF-1α/CXCR4 axis.
Recent exploration of combination therapies with CXCR4 antagonists have demonstrated improved outcomes, and abolishing the contribution of this pathway may prove crucial to effectively treat pancreatic cancer at both the primary tumor and metastases.
Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC.
CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer.
Further studies that define the role of CXCR4 signalling in PanIN progression will determine if CXCR4 could serve as a novel target for chemoprevention and early stage therapy in pancreatic cancer.
There was no overall association between pancreatic cancer risk and tumor necrosis factor-alpha (TNF-A -308G/A), regulated upon activation, normally T cell-expressed, and presumably secreted (RANTES -403G/A), and CC chemokine receptor 5 (CCR5-Delta32) polymorphisms.
Systemic administration of the selective CXCR4 inhibitor AMD 3100 effectively blocked the enhanced metastatic potential of CXCR4-expressing pancreatic cancer cells.
Using methylation-specific PCR, combined bisulfite restriction analysis, and bisulfite sequencing, we found the 5' CpG islands of the CXCR4 gene to be unmethylated in normal pancreas, whereas promoter hypermethylation was detected in 45% (9 of 20) of pancreatic cancer cell lines and in 46% (46 of 100) of primary pancreatic adenocarcinomas.
SDF-1 and its exclusive receptor, CXCR4, are reported to play important roles in tumor growth, angiogenesis and metastasis of different types of tumors such as breast, lung, prostate and pancreatic cancers.
The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others.
Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression through tumor cell migration and angiogenesis.