Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix.
Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix.
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DOI：
10.1002/1878-0261.13110
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发表时间：
2021-12
影响因子：
6.6
通讯作者：
Biffi S
中科院分区：
文献类型：
--
作者：
Bortot B;Apollonio M;Rampazzo E;Valle F;Brucale M;Ridolfi A;Ura B;Addobbati R;Di Lorenzo G;Romano F;Buonomo F;Ripepi C;Ricci G;Biffi S
恶性腹水在腹膜内转移发展中的确切作用尚不清楚，细胞外囊泡（EV）促进转移前小生境中肿瘤进展的机制尚未完全发现。在这项研究中，我们描述了高级别上皮性卵巢癌患者的腹水特征。从两个来源-大量腹水和腹水来源的肿瘤细胞培养物中分离出小EV（30-150 nm），并结合成像、蛋白质组学分析和蛋白质表达分析进行评估。此外，使用不同的数据库和生物信息学工具进行基因本体论和途径分析。结果证明，来自两个来源的小型电动汽车表现出显着不同的刚度和尺寸分布。大量腹水来源的小EV主要参与补体和凝血级联反应。来自腹水细胞培养物的小EV含有细胞外基质重塑调节剂的强大蛋白质组学谱，我们观察到新辅助化疗后转化生长因子-β-I（TGFβI），纤溶酶原激活物抑制剂1（派-1）和纤连蛋白表达增加。当在两个来源中测量时，我们证明了纤连蛋白在小EV中对化疗的反应中表现出相反的表达模式。这些发现强调了腹水细胞分离工作流程在研究治疗诱导的癌症适应过程中的重要性。细胞外囊泡（EV）在转移前小生境中促进卵巢癌进展的机制尚未完全发现。这项研究表明，在化疗前后采集腹水样本可以表征肿瘤细胞释放的小EV，反映其生物学状态。来自腹水来源的肿瘤细胞培养物的小EV含有细胞外基质重塑调节剂的稳健蛋白质组学谱。
The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre‐metastatic niche have not been fully discovered. In this study, we characterized ascites from high‐grade epithelial ovarian cancer patients. Small‐EVs (30–150 nm) were isolated from two sources—the bulk ascites and the ascitic fluid‐derived tumor cell cultures—and assessed with a combination of imaging, proteomic profiling, and protein expression analyses. In addition, Gene Ontology and pathway analysis were performed using different databases and bioinformatic tools. The results proved that the small‐EVs derived from the two sources exhibited significantly different stiffness and size distributions. The bulk ascitic fluid‐derived small‐EVs were predominantly involved in the complement and coagulation cascade. Small‐EVs derived from ascites cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators, and we observed an increase in transforming growth factor‐β‐I (TGFβI), plasminogen activator inhibitor 1 (PAI‐1), and fibronectin expression after neoadjuvant chemotherapy. When measured in the two sources, we demonstrated that fibronectin exhibited opposite expression patterns in small‐EVs in response to chemotherapy. These findings highlight the importance of an ascites cell isolation workflow in investigating the treatment‐induced cancer adaption processes. The mechanisms by which extracellular vesicles (EVs) promote ovarian cancer progression in the pre‐metastatic niche have not been fully discovered. This study showed that sampling ascites before and after chemotherapy allows characterizing small‐EVs released by tumor cells, reflecting their biological status. Small‐EVs derived from ascitic fluid‐derived tumor cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators.
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影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
45.3
作者：
Boehm, Steffen;Faruqi, Asma;Singh, Naveena
通讯作者：
Singh, Naveena
血小板对卵巢癌的影响。
影响因子：
4
作者：
Davis AN;Afshar-Kharghan V;Sood AK
通讯作者：
Sood AK
影响因子：
3.7
作者：
Latifi A;Luwor RB;Bilandzic M;Nazaretian S;Stenvers K;Pyman J;Zhu H;Thompson EW;Quinn MA;Findlay JK;Ahmed N
通讯作者：
Ahmed N
影响因子：
3
作者：
Huang, H.;Li, Y. J.;Liu, J. H.
通讯作者：
Liu, J. H.