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

IF 3.3 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Pituitary Pub Date : 2024-12-26 DOI:10.1007/s11102-024-01490-0

Carlos Alcaide, Francisco Perez, Francisco Esteban, Miguel Muñoz

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引用次数: 0

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.

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P物质和神经激肽-1受体在硬瘤性颅咽管瘤中的表达高于垂体。

背景：人颅咽管瘤（ACP）是一种起源于颅骨底部的脑肿瘤，具有局部侵袭性，可侵袭敏感结构，如视神经通路和下丘脑。传统的治疗方法是手术和放疗，随之而来的是严重的后遗症。众所周知，P物质（SP）肽和Neurokinin-1受体（NK-1R）参与炎症和癌症的进展，在临床前试验中，NK-1R拮抗剂阻断其可有效抑制肿瘤的发展。ACP的致癌机制是基于分泌表型，与分泌旁生物标志物的产生相关，这些生物标志物为ACP的进展建立了炎症和血管生成微环境。方法：为了解SP/NK-1R在ACP中的存在及分布，采用免疫组化方法对43例人ACP中SP和NK-1R的表达进行了研究，并与健康垂体样本进行了比较。结果：SP和NK-1R在所有ACP中均过表达，高于垂体。SP在肿瘤细胞的ACP中广泛表达，并优先定位于细胞核而不是细胞质。同样，神经胶质反应区和内皮细胞也在细胞核中优先表达SP。NK-1R主要在胶质反应中表达，特别是在其炎症细胞的细胞核和膜中表达，在细胞质中表达较少。在ACP新血管中，NK-1R在构成其基底膜的内皮细胞和成纤维细胞中表达。肿瘤细胞中NK-1R表达不明显。结论：本文首次报道了这些发现，提示SP和NK-1R在垂体和ACP中的作用，为未来使用NK-1R拮抗剂治疗ACP患者的临床试验打开了大门。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pituitary 医学-内分泌学与代谢

CiteScore

7.10

自引率

7.90%

发文量

审稿时长

6 months

期刊介绍： Pituitary is an international publication devoted to basic and clinical aspects of the pituitary gland. It is designed to publish original, high quality research in both basic and pituitary function as well as clinical pituitary disease. The journal considers: Biology of Pituitary Tumors Mechanisms of Pituitary Hormone Secretion Regulation of Pituitary Function Prospective Clinical Studies of Pituitary Disease Critical Basic and Clinical Reviews Pituitary is directed at basic investigators, physiologists, clinical adult and pediatric endocrinologists, neurosurgeons and reproductive endocrinologists interested in the broad field of the pituitary and its disorders. The Editorial Board has been drawn from international experts in basic and clinical endocrinology. The journal offers a rapid turnaround time for review of manuscripts, and the high standard of the journal is maintained by a selective peer-review process which aims to publish only the highest quality manuscripts. Pituitary will foster the publication of creative scholarship as it pertains to the pituitary and will provide a forum for basic scientists and clinicians to publish their high quality pituitary-related work.