Invasive and metastatic mechanisms of pancreatic cancer cells: the role of Glial Cell Line-Derived Neurotrophic Factor (GDNF), integrins, and NF-KappaB

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Perineural invasion is a prominent clinical feature of pancreatic cancer which difficulty in curative resection. The invasion system forms by multiple steps, but it has not cleared yet. In this study, we investigated the alteration of invasive ability by glial-cell-line-derived neurotrophic factor (GDNF) and the relationship between GDNF, integrin, and NF-kappaB.We used four human pancreatic cancer cells. We confirmed to express the receptors for GDNF. In the invasion assay, all human pancreatic cancer cells stimulated by GDNF increased the invasive ability for Extra Cellular Matrix. The invasive ability was inhibited by anti-receptors antibodies. The integrin subunits expressed in the all cell lines confirmed by the flow-cytometric analysis. In the cellular enzyme-linked immunosorbent assay, the integrin subunit of all cells expressed strongly under stimulating by GDNF and they were inhibited by anti-NF-kB antibody. NF-kappaB moving into the nuclear was enhanced in the all cells stimulated by GDNF. Similarly, after blocking the NF-kappaB, all cell lines showed a decreased ability to invade through the ECM proteins. In the all pancreatic cancer cells, the invasive ability appeared to increase under stimulating by GDNF and the signal of GDNF is transmitted through NF-kappaB.We conclude that GDNF, NF-kappaB and integrins have very important role for the invasive system of pancreatic cancer cells.