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通过癌症相关成纤维细胞优化子宫内膜癌细胞类器官的建立。

Optimization of endometrial cancer organoids establishment by cancer-associated fibroblasts.

机构信息

Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Gynecologic Minimally Invasive Surgery Research Center, Tongji University School of Medicine, Shanghai, China.

出版信息

Neoplasma. 2022 Jul;69(4):877-885. doi: 10.4149/neo_2022_211110N1597. Epub 2022 May 23.


DOI:10.4149/neo_2022_211110N1597
PMID:35603951
Abstract

Most endometrial cancers (EC) are diagnosed at an early stage with a favorable prognosis. However, for patients with advanced or recurrent disease, the chemotherapy response rate and overall survival remain poor. A novel in vitro model, tumor organoids, has important value in providing a more individualized treatment plan for tumor patients. However, the slow growth of the established EC organoid seriously hinders the application of EC organoids. Cancer-associated fibroblasts (CAFs), the main component of tumor stroma, have been reported to promote the proliferation of endometrial cancer cell lines and primary endometrial cancer cells in vivo and in vitro. Therefore, we optimized the current endometrial cancer organoid by introducing CAFs isolated from EC lesions. Here we developed long-term expandable organoids from endometrial cancer lesions, which show disease-associated traits and cancer-linked mutations. Based on the co-culture of CAFs and endometrial cancer organoids, we found that CAFs could promote the growth of endometrial cancer organoids, might by secreting factors according to the result that CAFs could also promote the growth. Our research provided a more promising model for the basic and preclinical study of endometrial cancer.

摘要

大多数子宫内膜癌 (EC) 在早期被诊断,预后良好。然而,对于晚期或复发性疾病患者,化疗反应率和总体生存率仍然较差。肿瘤类器官是一种新型的体外模型,它为肿瘤患者提供更个体化的治疗方案具有重要价值。然而,已建立的 EC 类器官的生长缓慢严重阻碍了 EC 类器官的应用。癌症相关成纤维细胞 (CAFs) 是肿瘤基质的主要成分,据报道,它们可以促进子宫内膜癌细胞系和原发性子宫内膜癌细胞在体内和体外的增殖。因此,我们通过引入从 EC 病变中分离出的 CAFs 对现有的子宫内膜癌类器官进行了优化。在这里,我们从子宫内膜癌病变中开发出了长期可扩增的类器官,它们显示出与疾病相关的特征和与癌症相关的突变。基于 CAFs 和子宫内膜癌类器官的共培养,我们发现 CAFs 可以促进子宫内膜癌类器官的生长,可能是通过分泌因子,因为 CAFs 也可以促进生长。我们的研究为子宫内膜癌的基础和临床前研究提供了一个更有前途的模型。

相似文献

[1]
Optimization of endometrial cancer organoids establishment by cancer-associated fibroblasts.

Neoplasma. 2022-7

[2]
Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis.

J Hematol Oncol. 2016-2-6

[3]
Cancer-associated fibroblasts promote proliferation of endometrial cancer cells.

PLoS One. 2013-7-26

[4]
Cancer-Associated Fibroblasts Provide a Stromal Niche for Liver Cancer Organoids That Confers Trophic Effects and Therapy Resistance.

Cell Mol Gastroenterol Hepatol. 2021

[5]
Organoid culture containing cancer cells and stromal cells reveals that podoplanin-positive cancer-associated fibroblasts enhance proliferation of lung cancer cells.

Lung Cancer. 2019-4-8

[6]
Cancer-Associated Fibroblasts Induce Epithelial-Mesenchymal Transition in Endometrial Cancer Cells by Regulating Pituitary Tumor Transforming Gene.

Cancer Invest. 2019

[7]
Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening.

Nat Cell Biol. 2019-8-1

[8]
Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome.

J Clin Endocrinol Metab. 2020-3-1

[9]
Cancer-associated fibroblasts nurture LGR5 marked liver tumor-initiating cells and promote their tumor formation, growth, and metastasis.

Cancer Med. 2023-9

[10]
Characterization and Clinical Relevance of Endometrial CAFs: Correlation between Post-Surgery Event and Resistance to Drugs.

Int J Mol Sci. 2023-3-29

引用本文的文献

[1]
Identification and Validation of a Novel Lactylation-related Gene Signature to Predict the Prognosis of Endometrial Cancer.

Discov Oncol. 2025-5-22

[2]
Organoid development and applications in gynecological cancers: the new stage of tumor treatment.

J Nanobiotechnology. 2025-1-16

[3]
Organoid modeling meets cancers of female reproductive tract.

Cell Death Discov. 2024-9-27

[4]
The use of organoids in creating immune microenvironments and treating gynecological tumors.

J Transl Med. 2024-9-23

[5]
Research progress on the application of organoids in gynecological tumors.

Front Pharmacol. 2024-6-26

[6]
Revolutionizing the female reproductive system research using microfluidic chip platform.

J Nanobiotechnology. 2023-12-19

[7]
Review on Advanced Cancer Modeling for a Cancer Study.

Curr Issues Mol Biol. 2022-10-31

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