维生素D衍生物抑制间皮细胞间充质转化和减轻卵巢癌的腹膜播散。

IF 1.1 4区 医学 Q3 PATHOLOGY
Medical Molecular Morphology Pub Date : 2025-09-01 Epub Date: 2025-02-18 DOI:10.1007/s00795-025-00424-4
Kazuhisa Fujita, Maia Hayashi, Masato Yoshihara, Satoshi Nomura, Kazuhisa Kitami, Emiri Miyamoto, Shohei Iyoshi, Kazumasa Mogi, Hiroki Fujimoto, Kaname Uno, Atsushi Kunishima, Yoshihiko Yamakita, Hiroyuki Tomita, Rino Tsutsumi, Ryota Sakamoto, Kazuo Nagasawa, Yusuke Masuo, Takumi Nishiuchi, Kiyosumi Shibata, Atsushi Enomoto, Hiroaki Kajiyama
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引用次数: 0

摘要

卵巢癌(OvCa)是妇科癌症相关死亡的主要原因,主要是由于腹膜播散,这促进了腹腔转移。本研究探讨了维生素D及其合成衍生物通过调节间皮细胞(MCs)的行为来减轻腹膜传播的潜力。已知维生素D通过其受体(VDR)影响癌症进展,我们的研究结果表明维生素D衍生物可以抑制TGF-β1诱导的MCs间质转化,TGF-β1是腹膜播散的关键驱动因素。本研究使用患者源性原代MCs和体内小鼠模型来评估维生素D衍生物对细胞形态、基因表达和OvCa细胞粘附的影响。两种维生素D衍生物VDR激动剂在维持上皮样MC形态、降低TGF-β1诱导的改变、抑制OvCa细胞粘附腹膜方面均表现出与骨化三醇相似的显著疗效。相反,VDR拮抗剂衍生物诱导MC细胞凋亡,强调维生素D在MC存活中的重要作用。这些发现表明,维生素D衍生物可以通过保持腹膜内稳态和防止转移而成为治疗OvCa的有希望的药物。需要进一步的研究来探索更广泛的衍生物及其潜在的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Vitamin D derivatives inhibit mesenchymal transition of mesothelial cells and mitigate peritoneal dissemination of ovarian cancer.

Ovarian cancer (OvCa) is a leading cause of gynecological cancer-related mortality, primarily due to peritoneal dissemination, which facilitates metastasis in the abdominal cavity. This study explored the potential of vitamin D and its synthetic derivatives in mitigating peritoneal dissemination by modulating the behavior of mesothelial cells (MCs). Vitamin D, through its receptor (VDR), is known to influence cancer progression, and our findings demonstrate that vitamin D derivatives can inhibit mesenchymal transition of MCs induced by TGF-β1, a key driver of peritoneal dissemination. This study used patient-derived primary MCs and in vivo mouse model to assess the effects of vitamin D derivatives on cell morphology, gene expression, and OvCa cell adhesion. Two vitamin D derivatives, VDR agonist, showed significant efficacy in maintaining epithelial-like MC morphology, reducing TGF-β1-induced changes, and inhibiting OvCa cell adhesion to the peritoneum, similar to calcitriol. Conversely, the VDR antagonist derivative induced MC apoptosis, highlighting the essential role of vitamin D in MC survival. These findings suggest that vitamin D derivatives could serve as promising therapeutic agents for OvCa by preserving peritoneal homeostasis and preventing metastasis. Further research is required to explore a broader range of derivatives and their underlying molecular mechanisms.

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来源期刊
Medical Molecular Morphology
Medical Molecular Morphology 医学-病理学
CiteScore
2.90
自引率
5.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.
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