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腹水来源的细胞外囊泡促进卵巢癌细胞的生长和迁移。

Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells.

机构信息

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

出版信息

Sci Rep. 2021 Apr 28;11(1):9149. doi: 10.1038/s41598-021-88163-1.

DOI:10.1038/s41598-021-88163-1
PMID:33911091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8080718/
Abstract

Ovarian cancer is associated with a high mortality rate due to diagnosis at advanced stages. Dissemination often occurs intraperitoneally within the ascites fluid. The microenvironment can support dissemination through several mechanisms. One potential ascites factor which may mediate dissemination are EVs or extracellular vesicles that can carry information in the form of miRNAs, proteins, lipids, and act as mediators of cellular communication. We present our observations on EVs isolated from ascitic supernatants from patients diagnosed with high grade serous ovarian carcinoma in augmenting motility, growth, and migration towards omental fat. MicroRNA profiling of EVs from malignant ascitic supernatant demonstrates high expression of miR 200c-3p, miR18a-5p, miR1246, and miR1290 and low expression of miR 100- 5p as compared to EVs isolated from benign ascitic supernatant. The migration of ovarian cancer spheroids towards omental fat is enhanced in the presence of malignant ascitic EVs. Gene expression of these cells showed increased expression of ZBED2, ZBTB20, ABCC3, UHMK1, and low expression of Transgelin and MARCKS. We present evidence that ovarian ascitic EVs increase the growth of ovarian cancer spheroids through miRNAs.

摘要

卵巢癌由于在晚期诊断，死亡率较高。扩散通常在腹腔内的腹水液中发生。微环境可以通过几种机制来支持扩散。一种潜在的腹水因子可能通过外泌体（EVs）或细胞外囊泡来介导扩散，这些囊泡可以携带 miRNA、蛋白质、脂质等形式的信息，并作为细胞间通讯的介质。我们展示了从高级别浆液性卵巢癌患者腹水中分离出的 EVs 的观察结果，这些 EVs 增强了向大网膜脂肪的运动、生长和迁移。与从良性腹水分离的 EVs 相比，恶性腹水 EVs 中的 microRNA 谱显示 miR 200c-3p、miR18a-5p、miR1246 和 miR1290 的表达较高，而 miR 100-5p 的表达较低。在恶性腹水 EVs 的存在下，卵巢癌细胞球体向大网膜脂肪的迁移增强。这些细胞的基因表达显示 ZBED2、ZBTB20、ABCC3、UHMK1 的表达增加，而 Transgelin 和 MARCKS 的表达降低。我们提出的证据表明，卵巢腹水 EVs 通过 miRNAs 增加了卵巢癌细胞球体的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/1940a74f1933/41598_2021_88163_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/cdcf44965958/41598_2021_88163_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/b5729e790c5a/41598_2021_88163_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/3654562e044f/41598_2021_88163_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/cd07d6a48d16/41598_2021_88163_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/52a1d87f00af/41598_2021_88163_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/1940a74f1933/41598_2021_88163_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/cdcf44965958/41598_2021_88163_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/b5729e790c5a/41598_2021_88163_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/3654562e044f/41598_2021_88163_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/cd07d6a48d16/41598_2021_88163_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/52a1d87f00af/41598_2021_88163_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1248/8080718/1940a74f1933/41598_2021_88163_Fig6_HTML.jpg

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