Alcaide Carlos, Perez Francisco, Esteban Francisco, Muñoz Miguel
Department of Pediatric Oncology, Hospital Regional Universitario de Málaga, Malaga, Spain.
Department of Pathology, Facultad de Medicina, Universidad Camilo José Cela / HM Hospitales, Madrid, Spain.
Pituitary. 2024 Dec 26;28(1):5. doi: 10.1007/s11102-024-01490-0.
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.
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.
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.
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.
人类造釉细胞瘤型颅咽管瘤（ACP）是一种起源于颅底的脑肿瘤，具有侵袭性的局部行为，可侵犯视神经通路和下丘脑等敏感结构。该肿瘤的传统治疗方法是手术和放疗，随之而来的是严重后遗症的发生。众所周知，P物质（SP）肽和神经激肽-1受体（NK-1R）参与炎症和癌症进展，在临床前试验中已表明用NK-1R拮抗剂阻断它们可有效对抗肿瘤发展。ACP的致癌机制基于一种分泌表型，该表型与旁分泌生物标志物的产生有关，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。
为了描述SP/NK-1R在ACP中的存在和分布，我们通过免疫组织化学研究了43例人类ACP中SP和NK-1R的表达，并与健康垂体样本进行了比较。
与垂体样本相比，所有ACP中SP和NK-1R均过度表达。在ACP中发现SP表达广泛，且优先定位于肿瘤细胞核而非细胞质中。同样，胶质反应区域和内皮细胞也优先在细胞核中表达SP。NK-1R主要在胶质反应中表达，尤其是在其炎症细胞的细胞核和细胞膜中，在细胞质中表达较少。在ACP新生血管中，NK-1R在内皮细胞和成纤维细胞中表达，这些细胞构成其基底膜。肿瘤细胞未显示明显的NK-1R表达。
这些首次在此报道的发现表明SP和NK-1R在垂体和ACP中发挥作用，并为未来对ACP患者使用NK-1R拮抗剂药物进行治疗的临床试验打开了大门。
