Enhanced tumor cell isolation by a biomimetic combination of E-selectin and anti-EpCAM: implications for the effective separation of circulating tumor cells (CTCs).
Enhanced tumor cell isolation by a biomimetic combination of E-selectin and anti-EpCAM: implications for the effective separation of circulating tumor cells (CTCs).
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DOI：
10.1021/la904678p
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发表时间：
2010-06-01
期刊：
影响因子：
--
通讯作者：
Hong S
中科院分区：
文献类型：
--
作者：
Myung JH;Launiere CA;Eddington DT;Hong S
选择性检测循环肿瘤细胞（CTC）对肿瘤转移的临床诊断和预后判断具有重要的临床意义。然而，主要由于患者血液中CTC的数量极低（低至109个血液细胞中的一个），有效检测和分离稀有细胞仍然是一个巨大的挑战。已知细胞滚动在生理过程中起关键作用，例如白细胞向炎症部位的募集和选择素介导的CTC转移。此外，由于CTC通常在表面上表达上皮细胞粘附分子（EpCAM），而正常血液细胞不表达，因此具有针对EpCAM的固定化抗体的底物可以特异性地与CTC相互作用。在本文中，我们创建了仿生表面功能化的P-和E-选择素和抗EpCAM诱导不同的反应的HL-60（在本研究中作为白细胞的模型）和MCF-7（CTC的模型）细胞。HL-60和MCF-7细胞在0.32 dyn/cm 2的剪切应力下表现出不同程度的与P-/E-选择素和抗EpCAM的相互作用。HL-60细胞在P-选择素固定的基质上以2.26 ± 0.28 μm/sec的速度滚动，而MCF-7细胞与基质没有相互作用。两种细胞系均与E-选择素相互作用，MCF-7细胞的滚动速度（4.24 ± 0.31 μm/sec）明显快于HL-60细胞（2.12 ± 0.15 μm/sec）。另一方面，只有MCF-7细胞与抗EpCAM包被的表面相互作用，在流动下形成固定结合。更重要的是，与通常用于CTC捕获的仅用抗EpCAM功能化的表面相比，滚动（E-选择素）和固定结合（抗EpCAM）的组合导致显著增强的分离能力和捕获效率（超过3倍增强）。我们的研究结果表明，细胞特异性检测和分离可以通过模拟组合的动态细胞滚动和静止结合的生物过程来实现，这将可能导致具有显著增强的特异性和灵敏度的CTC检测装置，而无需任何复杂的制造过程。
Selective detection of circulating tumor cells (CTCs) is of significant clinical importance for the clinical diagnosis and prognosis of cancer metastasis. However, largely due to the extremely low number of CTCs (as low as one in 109 hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. Cell rolling is known to play a key role in physiological processes such as recruitment of leukocytes to sites of inflammation and selectin-mediated CTC metastasis. Furthermore, as CTCs typically express epithelial-cell adhesion molecule (EpCAM) on the surface whereas normal hematologic cells do not, substrates with immobilized antibody against EpCAM may specifically interact with CTCs. In this paper, we created biomimetic surfaces functionalized with P- and E-selectin and anti-EpCAM that induce different responses of HL-60 (used as a model of leukocytes in this study) and MCF-7 (a model of CTCs) cells. HL-60 and MCF-7 cells showed different degrees of interaction with P-/E-selectin and anti-EpCAM at a shear stress of 0.32 dyn/cm2. HL-60 cells exhibited rolling on P-selectin-immobilized substrates at a velocity of 2.26 ± 0.28 μm/sec whereas MCF-7 cells had no interaction with the surface. Both cell lines, however, showed interactions with E-selectin, and the rolling velocity of MCF-7 cells (4.24 ± 0.31 μm/sec) was faster than that of HL-60 cells (2.12 ± 0.15 μm/sec). On the other hand, only MCF-7 cells interacted with anti-EpCAM-coated surfaces, forming stationary binding under flow. More importantly, the combination of the rolling (E-selectin) and stationary binding (anti-EpCAM) resulted in substantially enhanced separation capacity and capture efficiency (more than 3-fold enhancement), as compared to a surface functionalized solely with anti-EpCAM which has been commonly used for CTC capture. Our results indicate that cell-specific detection and separation may be achieved through mimicking the biological processes of combined dynamic cell rolling and stationary binding, which will likely lead to a CTC detection device with significantly enhanced specificity and sensitivity without any complex fabrication process.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
DOI：
10.1073/pnas.0404036101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Krivacic, RT;Ladanyi, A;Bruce, RH
通讯作者：
Bruce, RH
影响因子：
11.2
作者：
Dimitroff, CJ;Lechpammer, M;Kutok, JL
通讯作者：
Kutok, JL
影响因子：
2.2
作者：
NILSSON, R;SJOGREN, HO
通讯作者：
SJOGREN, HO
影响因子：
11.5
作者：
Danila, Daniel C.;Heller, Glenn;Scher, Howard I.
通讯作者：
Scher, Howard I.