Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis.
Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis.
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DOI：
10.1039/c4ib00015c
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Luker GD
中科院分区：
文献类型：
--
作者：
Cavnar SP;Ray P;Moudgil P;Chang SL;Luker KE;Linderman JJ;Takayama S;Luker GD
趋化因子在正常和病理状态下严格调节趋化性，但对多细胞相互作用如何产生细胞迁移所需的梯度的理解有限。以前的研究表明，趋化因子CXCL12趋化CXCR4+细胞的要求表达清道夫受体CXCR7在源-库系统。我们利用已建立的微流控装置发现，CXCR 4细胞对CXCL 12不同亚型的趋化性仅在CXCL 12水平高于最佳水平的条件下才需要CXCR 7清除。趋化性对CXCL12-β和-γ亚型，有更大的结合细胞外分子，并已在很大程度上被忽视，是依赖于CXCR7比更常见的研究CXCL12-α。在用FDA批准的CXCR4抑制剂治疗期间，CXCR4+细胞对甚至低水平的CXCL12-γ和CXCL12-β的趋化性仍然发生。我们还仅在晚期乳腺癌患者中检测到CXCL12-γ。装置内的生理梯度形成促进了对CXCL12亚型之间趋化性的关键差异的询问，并表明CXCL12-γ是转移性癌症的生物标志物。
Chemokines critically regulate chemotaxis in normal and pathologic states, but there is limited understanding of how multicellular interactions generate gradients needed for cell migration. Previous studies of chemotaxis of CXCR4+ cells toward chemokine CXCL12 suggest the requirement of cells expressing scavenger receptor CXCR7 in a source-sink system. We leveraged an established microfluidic device to discover that chemotaxis of CXCR4 cells toward distinct isoforms of CXCL12 required CXCR7 scavenging only under conditions with higher than optimal levels of CXCL12. Chemotaxis toward CXCL12-β and -γ isoforms, which have greater binding to extracellular molecules and have been largely overlooked, was less dependent on CXCR7 than the more commonly studied CXCL12-α. Chemotaxis of CXCR4+ cells toward even low levels of CXCL12-γ and CXCL12-β still occurred during treatment with a FDA-approved inhibitor of CXCR4. We also detected CXCL12-γ only in breast cancers from patients with advanced disease. Physiological gradient formation within the device facilitated interrogation of key differences in chemotaxis among CXCL12 isoforms and suggests CXCL12-γ as a biomarker for metastatic cancer.
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影响因子：
3.7
作者：
Kim BJ;Hannanta-anan P;Chau M;Kim YS;Swartz MA;Wu M
通讯作者：
Wu M
新型的CXCL12GAMMA同工型编码一个非结构化的阳离子结构域，该结构域调节了与糖胺聚糖和CXCR4的生物活性和相互作用。
影响因子：
3.7
作者：
Laguri, Cedric;Sadir, Rabia;Rueda, Patricia;Baleux, Francoise;Gans, Pierre;Arenzana-Seisdedos, Fernando;Lortat-Jacob, Hugues
通讯作者：
Lortat-Jacob, Hugues
DOI：
10.1073/pnas.1101133108
发表时间：
2011-10-25
影响因子：
11.1
作者：
Drury, Luke J.;Ziarek, Joshua J.;Dwinell, Michael B.
通讯作者：
Dwinell, Michael B.
影响因子：
3.4
作者：
Gleichmann, M;Gillen, C;Müller, HW
通讯作者：
Müller, HW
影响因子：
7.4
作者：
Luker, Kathryn E.;Gupta, Mudit;Luker, Gary D.
通讯作者：
Luker, Gary D.