Surface-templated hydrogel patterns prompt matrix-dependent migration of breast cancer cells towards chemokine-secreting cells.
Surface-templated hydrogel patterns prompt matrix-dependent migration of breast cancer cells towards chemokine-secreting cells.
复制标题
表面模板水凝胶图案促进乳腺癌细胞向趋化因子分泌细胞的基质依赖性迁移。
DOI：
10.1016/j.actbio.2014.11.033
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发表时间：
2015
影响因子：
9.7
通讯作者：
Takayama,Shuichi
中科院分区：
文献类型：
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作者：
Kojima,Taisuke;Moraes,Christopher;Cavnar,StephenP;Luker,GaryD;Takayama,Shuichi
本文描述了一种新的技术，用于制造空间定义的细胞负载胶原蛋白水凝胶，使用图图化，非粘性聚丙烯酰胺包被聚二甲基硅氧烷（PDMS）表面作为模板。用这种技术生成的乳腺癌细胞和趋化因子产生细胞的精确嵌入共培养模式揭示了癌细胞的基质依赖性和趋化因子异构体依赖性迁移。当3-D细胞外基质（ECM）包含结合分泌的CXCL12趋化因子的成分时，CXCL12趋化因子分泌细胞诱导癌细胞的趋化性显著增强。利用分泌具有不同基质亲和力的CXCL12异构体的细胞进行的实验观察和计算模拟表明，更强的配体-基质相互作用增强了趋化剂梯度，导致水凝胶中CXCL12梯度传感CXCR4受体表达（CXCR4+）细胞的趋化性增加。这些结果将我们最近关于CXCL12亚型依赖的趋化性研究从二维扩展到三维环境，并进一步揭示了ECM成分的重要作用。所开发的技术简单、通用、稳健；由于趋化剂与基质的相互作用是常见的，因此本文描述的方法应该广泛适用于研究许多不同类型细胞对各种趋化剂的生理迁移。
This paper describes a novel technique for fabricating spatially defined cell-laden collagen hydrogels, using patterned, non-adhesive polyacrylamide-coated polydimethylsiloxane (PDMS) surfaces as a template. Precisely patterned embedded co-cultures of breast cancer cells and chemokine-producing cells generated with this technique revealed matrix-dependent and chemokine isoform-dependent migration of cancer cells. CXCL12 chemokine-secreting cells induce significantly more chemotaxis of cancer cells when the 3-D extracellular matrix (ECM) includes components that bind the secreted CXCL12 chemokines. Experimental observations using cells that secrete CXCL12 isoforms with different matrix affinities together with computational simulations show that stronger ligand–matrix interactions sharpen chemoattractant gradients, leading to increased chemotaxis of the CXCL12 gradient-sensing CXCR4 receptor-expressing (CXCR4+) cells patterned in the hydrogel. These results extend our recent report on CXCL12 isoform-dependent chemotaxis studies from 2-D to 3-D environments and additionally reveal the important role of ECM composition. The developed technology is simple, versatile and robust; and as chemoattractant-matrix interactions are common, the methods described here should be broadly applicable for study of physiological migration of many different cell types in response to a variety of chemoattractants.