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Published on: June 30, 2023
Cathepsin D Inhibits Angiogenesis in Pituitary Neuroendocrine Tumors
Ren Fujiwara1,2, Hirotomo Ten3, Hui Chen4
1Graduate School of Medicine, International University of Health and Welfare, 4-3 Kozunomori, Narita, Chiba 286-8686, Japan.
Abstract:
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.
Insights
Cathepsin D and FGF2 significantly impact angiogenesis in pituitary tumors. Cathepsin D
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Prolactin and growth hormone fragments, vasoinhibins, possess anti-angiogenic properties.
- The roles of Cathepsin D and bone morphogenetic protein 1 (BMP-1) in vasohibin-mediated angiogenesis within pituitary neuroendocrine tumors (PitNETs) remain unclear.
- PitNETs exhibit altered angiogenesis, crucial for tumor growth and progression.
Purpose of the Study:
- To investigate the mechanism of action of Cathepsin D and BMP-1 on angiogenesis in PitNETs.
- To compare the effects of these enzymes with pro-angiogenic factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor-2 (FGF2).
Main Methods:
- Retrospective analysis of 43 patients with PitNETs.
- RNA extraction and analysis of mRNA and protein levels for Cathepsin D, BMP-1, VEGF, and FGF2 in 22 tumor samples.
- Assessment of von Willebrand factor to quantify vascularization in PitNETs.
Main Results:
- Cathepsin D and FGF2 showed significant correlations with vascularization in PitNETs.
- Both Cathepsin D and FGF2 are implicated in angiogenesis within PitNETs.
- Cathepsin D's anti-angiogenic effect was found to be dominant over FGF2's pro-angiogenic effect.
Conclusions:
- Cathepsin D and FGF2 play significant roles in regulating angiogenesis in PitNETs.
- Cathepsin D exhibits a dominant anti-angiogenic influence in the context of PitNET vascularization.
- Understanding these mechanisms may offer novel therapeutic targets for PitNETs.
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