Microfluidic platform for chemotaxis in gradients formed by CXCL12 source-sink cells.
Microfluidic platform for chemotaxis in gradients formed by CXCL12 source-sink cells.
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DOI：
10.1039/c0ib00041h
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Takayama S
中科院分区：
文献类型：
--
作者：
Torisawa YS;Mosadegh B;Bersano-Begey T;Steele JM;Luker KE;Luker GD;Takayama S
趋化因子CXCL12促进癌细胞依赖CXCR4向特定器官和组织的趋化性，导致转移性疾病。本研究旨在探究在细胞暴露于CXCL12梯度的生理条件下，表达CXCR7的细胞如何调节另一群CXCR4细胞的趋化性。我们通过在微通道中将表达CXCR4的癌细胞相对于产生CXCL12的细胞和表达CXCR7的细胞在空间上确定的位置进行排列，重现了癌症 - 基质微环境。CXCR7清除并降解CXCL12，这被认为是通过源 - 汇模型促进依赖CXCR4的趋化性。利用微通道装置，我们证明了CXCR4细胞的趋化性关键取决于CXCR7细胞（汇）相对于趋化因子分泌细胞（源）的存在和位置。此外，抑制迁移细胞上的CXCR4或汇细胞上的CXCR7阻断了朝向CXCL12的依赖CXCR4的趋化性，表明该装置能够识别通过靶向趋化因子清除受体来阻断迁移的新的治疗药物。我们的系统通过产生一个体外微环境，在这个环境中细胞产物可能随着趋化因子梯度的形成而分泌，从而在更浅但更生理的趋化因子梯度下实现有效的趋化性。除了阐明CXCL - 12介导的趋化性机制外，这种简单而可靠的方法可广泛用于构建多种微环境以研究细胞间通讯。
Chemokine CXCL12 promotes CXCR4-dependent chemotaxis of cancer cells to characteristic organs and tissues, leading to metastatic disease. This study was designed to investigate how cells expressing CXCR7 regulate chemotaxis of a separate population of CXCR4 cells under physiologic conditions in which cells are exposed to gradients of CXCL12. We recapitulated a cancer-stroma microenvironment by patterning CXCR4-expressing cancer cells in microchannels at spatially defined positions relative to CXCL12-producing cells and CXCR7-expressing cells. CXCR7 scavenges and degrades CXCL12, which has been proposed to facilitate CXCR4-dependent chemotaxis through a source-sink model. Using the microchannel device, we demonstrated that chemotaxis of CXCR4 cells depended critically on the presence and location of CXCR7 cells (sink) relative to chemokine secreting cells (source). Furthermore, inhibiting CXCR4 on migrating cells or CXCR7 on sink cells blocked CXCR4-dependent chemotaxis toward CXCL12, showing that the device can identify new therapeutic agents that block migration by targeting chemoattractant scavenging receptors. Our system enables efficient chemotaxis under much shallower yet more physiological chemoattractant gradients by generating an in vitro microenvironment where combinations of cellular products may be secreted along with formation of a chemoattractant gradient. In addition to elucidating mechanisms of CXCL-12 mediated chemotaxis, this simple and robust method can be broadly useful for engineering multiple microenvironments to investigate intercellular communication.
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DOI：
10.1039/b915965g
发表时间：
2009-12
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Torisawa YS;Mosadegh B;Luker GD;Morell M;O'Shea KS;Takayama S
通讯作者：
Takayama S
影响因子：
46.9
作者：
Jeon, NL;Baskaran, H;Toner, M
通讯作者：
Toner, M
影响因子：
--
作者：
Elbjeirami, WM;West, JL
通讯作者：
West, JL
影响因子：
3.8
作者：
Mosadegh, Bobak;Saadi, Wajeeh;Jeon, Noo Li
通讯作者：
Jeon, Noo Li
影响因子：
6.1
作者：
Torisawa, Yu-suke;Chueh, Bor-Han;Takayama, Shuichi
通讯作者：
Takayama, Shuichi