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卵巢癌细胞衍生的 JAGGED2 通过刺激间皮细胞中的 Notch 信号通路促进网膜转移。

Ovarian tumor cell-derived JAGGED2 promotes omental metastasis through stimulating the Notch signaling pathway in the mesothelial cells.

机构信息

Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

School of Medicine, Al-Faisal University, Riyadh, Saudi Arabia.

出版信息

Cell Death Dis. 2024 Apr 4;15(4):247. doi: 10.1038/s41419-024-06512-0.

DOI:10.1038/s41419-024-06512-0
PMID:38575576
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10995149/
Abstract

The primary site of metastasis for epithelial ovarian cancer (EOC) is the peritoneum, and it occurs through a multistep process that begins with adhesive contacts between cancer cells and mesothelial cells. Despite evidence that Notch signaling has a role in ovarian cancer, it is unclear how exactly it contributes to ovarian cancer omental metastasis, as well as the cellular dynamics and intrinsic pathways that drive this tropism. Here we show that tumor cells produced the Notch ligand Jagged2 is a clinically and functionally critical mediator of ovarian cancer omental metastasis by activating the Notch signaling in single-layered omental mesothelial cells. In turn, Jagged2 promotes tumor growth and therapeutic resistance by stimulating IL-6 release from mesothelial cells. Additionally, Jagged2 is a potent downstream mediator of the omental metastasis cytokine TGF-β that is released during omental destruction. Importantly, therapeutic inhibition of Jagged2-mediated omental metastasis was significantly improved by directly disrupting the Notch pathway in omental mesothelial cells. These findings highlight the key role of Jagged2 to the functional interplay between the TGF-β and the Notch signaling pathways during the metastatic process of ovarian cancer cells to the omentum and identify the Notch signaling molecule as a precision therapeutic target for ovarian cancer metastasis.

摘要

上皮性卵巢癌（EOC）的主要转移部位是腹膜，它通过一个多步骤的过程发生，该过程始于癌细胞与间皮细胞之间的黏附接触。尽管有证据表明 Notch 信号在卵巢癌中起作用，但它如何确切地促进卵巢癌网膜转移，以及驱动这种趋向性的细胞动力学和内在途径尚不清楚。在这里，我们表明肿瘤细胞产生的 Notch 配体 Jagged2 通过激活单层网膜间皮细胞中的 Notch 信号，是卵巢癌网膜转移的临床和功能关键介质。反过来，Jagged2 通过刺激间皮细胞释放 IL-6 来促进肿瘤生长和治疗耐药性。此外，Jagged2 是 TGF-β的一种有效的下游介质，TGF-β在网膜破坏期间释放。重要的是，通过直接破坏网膜间皮细胞中的 Notch 途径，Jagged2 介导的网膜转移的治疗抑制作用得到显著改善。这些发现强调了 Jagged2 在卵巢癌细胞转移到网膜的过程中 TGF-β和 Notch 信号通路之间的功能相互作用中的关键作用，并将 Notch 信号分子鉴定为卵巢癌转移的精确治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/391fa1b26830/41419_2024_6512_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/e4cc52826c68/41419_2024_6512_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/d5e1bda1befc/41419_2024_6512_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/f0c7a59fdb8a/41419_2024_6512_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/a996230129c0/41419_2024_6512_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/e786fd770cfc/41419_2024_6512_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/391fa1b26830/41419_2024_6512_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/e4cc52826c68/41419_2024_6512_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/4c99f9c77653/41419_2024_6512_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/22fa276771f0/41419_2024_6512_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/d7a7343b93fe/41419_2024_6512_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/10f12a7d2ecc/41419_2024_6512_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/d5e1bda1befc/41419_2024_6512_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/f0c7a59fdb8a/41419_2024_6512_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/a996230129c0/41419_2024_6512_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/e786fd770cfc/41419_2024_6512_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5648/10995149/391fa1b26830/41419_2024_6512_Fig10_HTML.jpg

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本文引用的文献

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J Clin Invest. 2021 Aug 16;131(16). doi: 10.1172/JCI146186.
2
Leveraging microenvironmental synthetic lethalities to treat cancer.利用微环境合成致死性治疗癌症。
J Clin Invest. 2021 Mar 15;131(6). doi: 10.1172/JCI143765.
3
TGFβ signaling networks in ovarian cancer progression and plasticity.TGFβ 信号通路在卵巢癌进展和可塑性中的作用。
Clin Exp Metastasis. 2021 Apr;38(2):139-161. doi: 10.1007/s10585-021-10077-z. Epub 2021 Feb 15.
4
Omental metastasis as a predictive risk factor for unfavorable prognosis in patients with stage III-IV epithelial ovarian cancer.大网膜转移作为 III-IV 期上皮性卵巢癌患者预后不良的预测风险因素。
Int J Clin Oncol. 2021 May;26(5):995-1004. doi: 10.1007/s10147-021-01866-3. Epub 2021 Jan 29.
5
Neutralization of TGFβ Improves Tumor Immunity and Reduces Tumor Progression in Ovarian Carcinoma.中和 TGFβ 可改善卵巢癌的肿瘤免疫并抑制肿瘤进展。
Mol Cancer Ther. 2021 Mar;20(3):602-611. doi: 10.1158/1535-7163.MCT-20-0412. Epub 2020 Dec 15.
6
Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer.肿瘤相关中性粒细胞通过 Jagged2 激活在卵巢癌中协调肿瘤内 IL-8 驱动的免疫逃逸。
Br J Cancer. 2020 Oct;123(9):1404-1416. doi: 10.1038/s41416-020-1026-0. Epub 2020 Aug 11.
7
Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer.大网膜组织驻留巨噬细胞促进卵巢癌的转移扩散。
J Exp Med. 2020 Apr 6;217(4). doi: 10.1084/jem.20191869.
8
Sequential combination of cisplatin with eugenol targets ovarian cancer stem cells through the Notch-Hes1 signalling pathway.顺铂联合丁香酚通过 Notch-Hes1 信号通路靶向卵巢癌干细胞。
J Exp Clin Cancer Res. 2019 Aug 30;38(1):382. doi: 10.1186/s13046-019-1360-3.
9
Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity.缺氧诱导的表型介导肿瘤异质性。
Adv Exp Med Biol. 2019;1136:43-55. doi: 10.1007/978-3-030-12734-3_3.
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J Exp Med. 2019 Jan 7;216(1):176-194. doi: 10.1084/jem.20181170. Epub 2018 Dec 19.