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Probing 3D Collective Cancer Invasion Using Double-Stranded Locked Nucleic Acid Biosensors

机译:使用双链锁定核酸生物传感器探测3D集体癌症入侵

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Cancer is a leading cause of death worldwide and metastases are responsible for over 90% of human cancer deaths. There is an urgent need to develop novel therapeutics for suppressing cancer invasion, the initial step of metastasis. Nevertheless, the regulation of cancer invasion is poorly understood due to a paucity of tools for monitoring the invasion process in 3D microenvironments. Here, we report a double-stranded locked nucleic acid (dsLNA). biosensor for investigating 3D collective cancer invasion. By incorporating multiphoton microscopy and the dsLNA biosensor, we perform dynamic single cell gene expression analysis while simultaneously characterizing the biomechanical interaction between the invading sprouts and the extracellular matrix. Gene profiling of invasive leader cells and detached cells suggest distinctive signaling mechanisms involved in collective and individual invasion in the 3D microenvironment. Our results underscore the involvement of Notch signaling in 3D collective cancer invasion, which warrants further investigation toward antimetastasis therapy in the future.
机译:癌症是世界范围内主要的死亡原因,而转移是导致90%以上的人类癌症死亡的原因。迫切需要开发新的疗法来抑制癌症的侵袭,这是转移的第一步。然而,由于缺乏用于监视3D微环境中的侵袭过程的工具,因此对癌症侵袭的调控了解甚少。在这里,我们报告双链锁核酸(dsLNA)。用于研究3D集体癌症入侵的生物传感器。通过结合多光子显微镜和dsLNA生物传感器,我们进行动态单细胞基因表达分析,同时表征入侵的新芽和细胞外基质之间的生物力学相互作用。侵袭性前导细胞和脱离细胞的基因分析表明,与3D微环境中的集体和个体入侵有关的独特信号机制。我们的结果强调了Notch信号参与3D集体癌症侵袭的情况,这有必要在将来进行抗转移治疗的进一步研究。

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