Involvement of substance P and the NK-1 receptor in pancreatic cancer

Abstract

Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1- and 5-year relative survival rates are 25% and 6%, respectively. Thus, it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients. The peptide substance P (SP) has a widespread distribution throughout the body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates biological functions related to cancer, such as tumor cell proliferation, neoangiogenesis, the migration of tumor cells for invasion, infiltration and metastasis, and it exerts an antiapoptotic effects on tumor cells. It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression: (1) pancreatic cancer cells and samples express NK-1 receptors; (2) the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells; (3) nanomolar concentrations of SP induce pancreatic cancer cell proliferation; (4) NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner, at a certain concentration, these antagonists inhibit 100% of tumor cells; (5) this antitumor action is mediated through the NK-1 receptor, and tumor cells die by apoptosis; and (6) NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts. All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer; that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer, and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.