In a new study reported in the Journal of Clinical Investigation, researchers from The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) have identified a substance called Gdf-15 released by pancreatic cancer cells that protect them from attack by immune cells called macrophages.
The study found that the substance might be required for the development of early pancreatic tumours. The research also revealed that a molecule pronounced N-F-kappa-B (NF-kB) helps tumour cells produce Gdf-15. When macrophages take up Gdf-15, it prevents them making nitric oxide and tumour necrosis factor, two chemicals they release to kill cancer cells.
Ironically, the researchers found that NF-kB in macrophages plays an important role in the production of nitric oxide and tumour necrosis factor. The principal investigator Denis Guttridge, PhD, professor of Cancer Biology and Genetics at Ohio State and associate director for basic research said, “This study shows that GDF-15 plays an important role in the development of pancreatic cancer and might be required for the development of early pancreatic tumours.”
Guttridge added that the researchers believe that this mechanism of disarming macrophages develops early in cancer cells, enabling small tumours to survive and grow. These findings support the need for preclinical studies to determine the role of GDF-15 in the development of pancreatic cancer."
The team conducted the study using pancreatic cancer cell lines, cells from patient tumours and an animal model. The study outcomes included NF-kB is a direct regulator of Gdf-15; GDF-15 suppresses macrophage cell-killing activity by inhibiting the production of nitric oxide and tumour necrosis factor; Both GDF-15 and NF-kB are overexpressed in patients with pancreatic cancer.
Overall, the study results reveal that NF-kB is responsible for the synthesis and secretion of GDF-15 from pancreatic tumour cells, and that GDF-15 then inhibits NF-kB activity in macrophages and blocks them from killing tumour cells, Guttridge concluded.