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子宫内膜异位症细胞球体以与卵巢癌细胞球体相似的方式进行间皮清除。

Endometriosis Cell Spheroids Undergo Mesothelial Clearance in a Similar Manner to Ovarian Cancer Cell Spheroids.

作者信息

Kloeckner Allison A, Walker Sarah R

机构信息

Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH 03824, USA.

出版信息

Cells. 2025 May 19;14(10):742. doi: 10.3390/cells14100742.

DOI:10.3390/cells14100742
PMID:40422245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12110144/
Abstract

Endometriosis is a gynecological disease characterized by the presence of endometrium-like cells located outside the uterus. The most widely accepted theory for endometriosis development, retrograde menstruation, does not account for extra-pelvic lesions or ones found on other organs in the peritoneal cavity. Similar to ovarian cancer, endometriosis cells can interact with the mesothelial cells of the peritoneal cavity. In ovarian cancer metastasis, ovarian cancer cell spheroids attach and push away the mesothelial cells lining the peritoneal cavity, clearing the mesothelial layer. Since endometriosis cells are known to interact with the mesothelium, we hypothesized that endometriosis cells would be able to form spheroids capable of undergoing mesothelial clearance. To test this, we designed an in vitro mesothelial clearance assay using endometriosis spheroids and a mesothelial cell monolayer. Our results demonstrate that normal and endometriotic epithelial cell spheroids can perform mesothelial clearance similar to ovarian cancer spheroids, though normal endometrial cells do not clear as well as endometriosis cells. Additionally, we demonstrated that our mesothelial clearance assay can test potential pharmacological therapies for endometriosis prior to clinical trials. These results give insight into the development of endometriosis lesions, but further research is needed to determine the mechanisms behind mesothelial clearance in endometriosis.

摘要

子宫内膜异位症是一种妇科疾病,其特征是子宫外存在类似子宫内膜的细胞。关于子宫内膜异位症发展最广泛接受的理论——经血逆流,无法解释盆腔外病变或在腹膜腔其他器官上发现的病变。与卵巢癌相似,子宫内膜异位症细胞可与腹膜腔的间皮细胞相互作用。在卵巢癌转移过程中,卵巢癌细胞球体附着并推开腹膜腔内衬的间皮细胞,清除间皮层。由于已知子宫内膜异位症细胞与间皮相互作用,我们假设子宫内膜异位症细胞能够形成能够进行间皮清除的球体。为了验证这一点,我们设计了一种使用子宫内膜异位症球体和间皮细胞单层的体外间皮清除试验。我们的结果表明,正常和子宫内膜异位上皮细胞球体能够进行类似于卵巢癌细胞球体的间皮清除,尽管正常子宫内膜细胞的清除效果不如子宫内膜异位症细胞。此外,我们证明我们的间皮清除试验可以在临床试验之前测试子宫内膜异位症的潜在药物治疗方法。这些结果为子宫内膜异位症病变的发展提供了见解,但需要进一步研究以确定子宫内膜异位症中间皮清除背后的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/8654a260bd2d/cells-14-00742-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/d74cd8b7c222/cells-14-00742-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/152b0cf96884/cells-14-00742-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/966613e291e7/cells-14-00742-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/bf1dbbc4932c/cells-14-00742-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/e296951e3ba1/cells-14-00742-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/6386ecff8ba7/cells-14-00742-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/dcc3b343b50b/cells-14-00742-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/8654a260bd2d/cells-14-00742-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/d74cd8b7c222/cells-14-00742-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/152b0cf96884/cells-14-00742-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/966613e291e7/cells-14-00742-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/bf1dbbc4932c/cells-14-00742-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/e296951e3ba1/cells-14-00742-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/6386ecff8ba7/cells-14-00742-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/dcc3b343b50b/cells-14-00742-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef7/12110144/8654a260bd2d/cells-14-00742-g008.jpg

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本文引用的文献

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Endometriosis and the Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Pathophysiology: A Narrative Review of the Literature.子宫内膜异位症及促炎和抗炎细胞因子在病理生理学中的作用:文献综述
Diagnostics (Basel). 2024 Jan 31;14(3):312. doi: 10.3390/diagnostics14030312.
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Transcriptional Landscape of 3D vs. 2D Ovarian Cancer Cell Models.3D与2D卵巢癌细胞模型的转录图谱
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Spheroids as a model for endometriotic lesions.球体作为子宫内膜病变的模型。
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Persistent activation of signal transducer and activator of transcription 3 via interleukin-6 trans-signaling is involved in fibrosis of endometriosis.白细胞介素 6 转导信号通过信号转导子和转录激活子 3 的持续激活参与子宫内膜异位症的纤维化。
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Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine.卵巢癌的三维建模:从细胞系到类器官用于发现和个性化医疗
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Pathogenesis Based Diagnosis and Treatment of Endometriosis.基于发病机制的子宫内膜异位症的诊断与治疗。
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Topological defects in the mesothelium suppress ovarian cancer cell clearance.间皮中的拓扑缺陷抑制卵巢癌细胞清除。
APL Bioeng. 2021 Aug 3;5(3):036103. doi: 10.1063/5.0047523. eCollection 2021 Sep.
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A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.一种新型的人子宫内膜上皮细胞系,可用于妇科疾病建模和药物筛选。
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Statins: a repurposed drug to fight cancer.他汀类药物:一种用于抗癌的再利用药物。
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