Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis.
Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis.
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DOI：
10.3389/fbioe.2020.611802
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发表时间：
2020
影响因子：
5.7
通讯作者：
Choi JW
中科院分区：
文献类型：
--
作者：
Cho HY;Choi JH;Kim KJ;Shin M;Choi JW
转移是导致大量癌症相关死亡的主要原因。通过描绘体外转移过程的精确环境，微流控系统为癌细胞迁移、侵袭、定植和补充营养物质的获取提供了有用的见解。然而，目前的体外转移模型对基于血管的转移途径的研究存在偏颇，对与炎症系统密切相关的淋巴道转移的认识有限。为了了解炎性细胞因子在淋巴转移中的作用，我们开发了一个模拟淋巴管-组织-血管(LTB)结构的三通道微流控系统。基于LTB芯片，我们成功地证实了淋巴转移过程中肿瘤微环境中炎症细胞因子白介素6(IL-6)介导的细胞间通讯。IL-6作用于不同亚型的乳腺癌细胞可诱导上皮-间充质转化(EMT)，并改善组织侵袭性(8倍)。IL-6作用下的人淋巴管内皮细胞分泌血管内皮生长因子，观察血管内皮细胞向淋巴管通道的生长。LTB芯片可用于分析淋巴转移过程中的细胞间通讯，是了解肿瘤微环境中炎性细胞因子、间质反应、缺氧和营养缺乏等细胞外刺激下细胞间通讯的独特工具。
Metastasis is the primary cause of a large number of cancer-associated deaths. By portraying the precise environment of the metastasis process in vitro, the microfluidic system provides useful insights on the mechanisms underlying cancer cell migration, invasion, colonization, and the procurement of supplemental nutrients. However, current in vitro metastasis models are biased in studying blood vessel-based metastasis pathways and thus the understanding of lymphatic metastasis is limited which is also closely related to the inflammatory system. To understand the effects of inflammatory cytokines in lymphatic metastasis, we developed a three-channel microfluidic system by mimicking the lymph vessel-tissue-blood vessel (LTB) structure. Based on the LTB chip, we successfully confirmed the inflammatory cytokine, interleukin 6 (IL-6), -mediated intercellular communication in the tumor microenvironment during lymphatic metastasis. The IL-6 exposure to different subtypes of breast cancer cells was induced epithelial-mesenchymal transition (EMT) and improved tissue invasion property (8-fold). And the growth of human vein endothelial cells toward the lymph vessel channel was observed by VEGF secretion from human lymphatic endothelial cells with IL-6 treatment. The proposed LTB chip can be applied to analyze the intercellular communication during the lymphatic metastasis process and be a unique tool to understand the intercellular communication in the cancer microenvironment under various extracellular stimuli such as inflammatory cytokines, stromal reactions, hypoxia, and nutrient deficiency.
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影响因子：
3.7
作者：
Matsuoka J;Yashiro M;Doi Y;Fuyuhiro Y;Kato Y;Shinto O;Noda S;Kashiwagi S;Aomatsu N;Hirakawa T;Hasegawa T;Shimizu K;Shimizu T;Miwa A;Yamada N;Sawada T;Hirakawa K
通讯作者：
Hirakawa K
影响因子：
11.7
作者：
Kim YH;Jung E;Im GB;Kim YJ;Kim SW;Jeong GJ;Jang YC;Park KM;Kim DI;Yu T;Bhang SH
通讯作者：
Bhang SH
肿瘤内皮细胞共培养及微流控相互作用的进展
影响因子：
8.8
作者：
Li W;Khan M;Mao S;Feng S;Lin JM
通讯作者：
Lin JM
影响因子：
8
作者：
Pang MF;Georgoudaki AM;Lambut L;Johansson J;Tabor V;Hagikura K;Jin Y;Jansson M;Alexander JS;Nelson CM;Jakobsson L;Betsholtz C;Sund M;Karlsson MC;Fuxe J
通讯作者：
Fuxe J
影响因子：
15.3
作者：
Recouvreux, Maria Victoria;Moldenhauer, Matthew R.;Commisso, Cosimo
通讯作者：
Commisso, Cosimo