Fujiwara Ren, Ten Hirotomo, Chen Hui, Jiang Chuan-Lu, Oyama Ken-Ichi, Onoda Keisuke, Matsuno Akira
Graduate School of Medicine, International University of Health and Welfare, 4-3 Kozunomori, Narita, Chiba 286-8686, Japan.
Department of Neurosurgery, International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita, Chiba 286-8520, Japan.
Acta Histochem Cytochem. 2022 Dec 28;55(6):203-211. doi: 10.1267/ahc.22-00098. Epub 2022 Dec 20.
Prolactin and growth hormone can acquire anti-angiogenic properties after undergoing proteolytic cleavage by Cathepsin D and bone morphogenetic protein 1 (BMP-1) into fragments known as vasoinhibins. Little is known about the effect of vasoinhibins on angiogenesis through the involvement of key cleavage enzymes Cathepsin D and BMP-1 in pituitary neuroendocrine tumors (PitNETs, formerly pituitary adenomas). The purpose of this study was to investigate the mechanism of action of Cathepsin D and BMP-1 on angiogenesis in PitNETs compared with that of pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor-2 (FGF2). A total of 43 patients were enrolled in a retrospective analysis and 22 samples were suitable for RNA extraction, including 16 nonfunctional PitNETs and six somatotroph tumors. The mRNA and protein levels of Cathepsin D, BMP-1, VEGF, and FGF2 were compared with those of von Willebrand factor, which was assessed to determine the vascularization of PitNETs. Cathepsin D and FGF2 were significantly correlated with vascularization in PitNETs. Both Cathepsin D and FGF2 are highly involved in angiogenesis in PitNETs, although the effect of Cathepsin D as an anti-angiogenic factor is dominant over that of FGF2 as a pro-angiogenic factor.
催乳素和生长激素在被组织蛋白酶D和骨形态发生蛋白1（BMP-1）进行蛋白水解切割后可获得抗血管生成特性，形成被称为血管抑制素的片段。关于血管抑制素通过关键切割酶组织蛋白酶D和BMP-1参与垂体神经内分泌肿瘤（PitNETs，以前称为垂体腺瘤）对血管生成的影响，人们了解甚少。本研究的目的是探讨与促血管生成因子（包括血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子-2（FGF2））相比，组织蛋白酶D和BMP-1在PitNETs血管生成中的作用机制。共有43例患者纳入回顾性分析，22个样本适合进行RNA提取，包括16例无功能PitNETs和6例生长激素瘤。将组织蛋白酶D、BMP-1、VEGF和FGF2的mRNA和蛋白水平与血管性血友病因子的水平进行比较，后者用于评估PitNETs的血管化情况。组织蛋白酶D和FGF2与PitNETs的血管化显著相关。组织蛋白酶D和FGF2均高度参与PitNETs的血管生成，尽管组织蛋白酶D作为抗血管生成因子的作用比FGF2作为促血管生成因子的作用更显著。
