Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.
Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.
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DOI：
10.18632/aging.101355
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发表时间：
2017-12-28
期刊：
影响因子：
--
通讯作者：
Mirnezami AH
中科院分区：
文献类型：
--
作者：
Bhome R;Goh RW;Bullock MD;Pillar N;Thirdborough SM;Mellone M;Mirnezami R;Galea D;Veselkov K;Gu Q;Underwood TJ;Primrose JN;De Wever O;Shomron N;Sayan AE;Mirnezami AH
结直肠癌是一种发病率不断上升的全球性疾病。死亡率很大程度上归因于转移性扩散，因此，需要对影响肿瘤进展的信号进行机械解剖。肿瘤基质在肿瘤的增殖、侵袭和耐药过程中起着至关重要的作用。在这里，我们试图识别和表征外泌体microrna作为基质肿瘤信号传导的介质。在体外，我们证明成纤维细胞外泌体被转移到结直肠癌细胞中，导致细胞microRNA水平增加，影响增殖和化疗耐药。为了进一步探讨这一点，从一项正在进行的前瞻性生物标志物研究中，从配对的患者来源的正常和癌症相关成纤维细胞中分析了外泌体microrna。外泌体癌症相关成纤维细胞特征由microrna 329、181a、199b、382、215和21组成。其中，miR-21丰度最高，在外泌体中富集。与对照组成纤维细胞相比，用过表达mir -21的成纤维细胞和CRC细胞建立的原位异种移植物导致肝转移增加。我们的数据提供了一种新的结直肠癌基质外泌体特征，具有生物标志物验证的潜力。此外，我们通过原位模型证实了间质miR-21在结直肠癌进展中的重要性，并提出外泌体是miR-21在间质成纤维细胞和癌细胞之间转移的载体。
Colorectal cancer is a global disease with increasing incidence. Mortality is largely attributed to metastatic spread and therefore, a mechanistic dissection of the signals which influence tumor progression is needed. Cancer stroma plays a critical role in tumor proliferation, invasion and chemoresistance. Here, we sought to identify and characterize exosomal microRNAs as mediators of stromal-tumor signaling. In vitro, we demonstrated that fibroblast exosomes are transferred to colorectal cancer cells, with a resultant increase in cellular microRNA levels, impacting proliferation and chemoresistance. To probe this further, exosomal microRNAs were profiled from paired patient-derived normal and cancer-associated fibroblasts, from an ongoing prospective biomarker study. An exosomal cancer-associated fibroblast signature consisting of microRNAs 329, 181a, 199b, 382, 215 and 21 was identified. Of these, miR-21 had highest abundance and was enriched in exosomes. Orthotopic xenografts established with miR-21-overexpressing fibroblasts and CRC cells led to increased liver metastases compared to those established with control fibroblasts. Our data provide a novel stromal exosome signature in colorectal cancer, which has potential for biomarker validation. Furthermore, we confirmed the importance of stromal miR-21 in colorectal cancer progression using an orthotopic model, and propose that exosomes are a vehicle for miR-21 transfer between stromal fibroblasts and cancer cells.
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影响因子：
64.5
作者：
Boelens MC;Wu TJ;Nabet BY;Xu B;Qiu Y;Yoon T;Azzam DJ;Twyman-Saint Victor C;Wiemann BZ;Ishwaran H;Ter Brugge PJ;Jonkers J;Slingerland J;Minn AJ
通讯作者：
Minn AJ
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
DOI：
10.1016/j.nhtm.2016.03.001
发表时间：
2016-01
期刊：
New horizons in translational medicine
影响因子：
--
作者：
Bhome R;Al Saihati HA;Goh RW;Bullock MD;Primrose JN;Thomas GJ;Sayan AE;Mirnezami AH
通讯作者：
Mirnezami AH
影响因子：
5.5
作者：
Bhome R;Bullock MD;Al Saihati HA;Goh RW;Primrose JN;Sayan AE;Mirnezami AH
通讯作者：
Mirnezami AH
影响因子：
8.8
作者：
Calvo F;Ranftl R;Hooper S;Farrugia AJ;Moeendarbary E;Bruckbauer A;Batista F;Charras G;Sahai E
通讯作者：
Sahai E