Cathepsin D Inhibits Angiogenesis in Pituitary Neuroendocrine Tumors

作者:Matsuno, Akira*; Fujiwara, Ren; Ten, Hirotomo; Chen, Hui; Jiang, Chuan-lu; Oyama, Ken-ichi; Onoda, Keisuke
来源:Acta Histochemica et Cytochemica, 2022, 55(6): 203-211.
DOI:10.1267/ahc.22-00098

摘要

Prolactin and growth hormone can acquire anti-angiogenic properties after undergoing pro-teolytic 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 neu-roendocrine 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 non-functional 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.

  • 单位
    哈尔滨医科大学; 1

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