Substance P and Neurokinin-1 receptor are overexpressed in adamantinomatous craniopharyngioma than in the pituitary gland

Abstract

Background: Human adamantinomatous craniopharyngioma (ACP) is a brain tumor that originates at the base of the skull and shows aggressive local behavior, invading sensitive structures such as the optic pathways and hypothalamus. The conventional treatment of the tumor has been surgery and radiotherapy with the consequent development of serious sequelae. It is well known that Substance P (SP) peptide and Neurokinin-1 receptor (NK-1R) are involved in inflammation and cancer progression and its blockage with NK-1R antagonists has been shown to effectively counteract tumor development in preclinical trials. The oncogenic mechanism underlying ACP is based on a secretory phenotype associated with the production of paracrine biomarkers that establish an inflammatory and angiogenic microenvironment for the progression of ACP.

Methods: With the aim of describing the existence and distribution of SP/NK-1R in the ACP, we studied by immunohistochemistry the expression of SP and NK-1R in 43 human ACP and compared with healthy pituitary gland samples.

Results: SP and the NK-1R were overexpressed in all ACP more than in pituitary glands samples. SP expression is found widespread the ACP and is preferentially localized in the nucleus than in cytoplasm of tumor cells. Likewise, areas of glial reaction and endothelial cells also express SP preferentially in the cell nuclei. NK-1R is expressed mainly in the glial reaction, especially in the nuclei and membranes of its inflammatory cells and less prominently in the cytoplasm. In ACP neovessels, NK-1R is expressed in endothelial cells and fibroblasts that constitute their basement membranes. Tumor cells did not show significant NK-1R expression.

Conclusions: These findings, reported here for the first time, suggest a role for SP and NK-1R in pituitary gland and ACP and opens the door to future clinical trials on treatment with NK-1R antagonist drugs in ACP patients.

Keywords: Craniopharyngioma; Immunohistochemistry; Neurokinin-1 receptor; Pituitary gland; Substance P.