Biophysical Phenotyping and Modulation of ALDH plus Inflammatory Breast Cancer Stem-Like Cells
Biophysical Phenotyping and Modulation of ALDH plus Inflammatory Breast Cancer Stem-Like Cells
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DOI：
10.1002/smll.201802891
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发表时间：
2019-02-01
期刊：
影响因子：
13.3
通讯作者：
Fu, Jianping
中科院分区：
文献类型：
--
作者：
Chen, Weiqiang;Allen, Steven G.;Fu, Jianping
癌症干细胞样细胞（CSC）已被证明可以启动许多癌症类型的肿瘤发生和癌症转移。尽管通过特定标记物表达识别 CSC 有助于定义 CSC 区室，但它并不能直接提供有关该癌细胞亚群如何或为何更具转移性或致瘤性的信息。在这项研究中，使用多种微工程工具全面描述了单细胞水平上侵袭性和致死性炎症性乳腺癌 (IBC) CSC 的功能和生物物理特征。与 ALDH-非 CSC 相比，ALDH+ SUM149 IBC CSC 具有独特的功能（细胞迁移、生长、粘附、侵袭和自我更新）和生物物理（细胞变形性、粘附强度和收缩性）特性，这为解释 CSC 为何具有增强的转移倾向提供了生物物理学见解。进一步表明细胞生物物理表型可以预测和决定IBC细胞的致瘤能力。通过生物物理属性（粘附性和硬度）选择和调节的 SUM149 和 SUM159 IBC 细胞在体外显示出 CSC 的特征，并在原发性肿瘤生长的体内小鼠模型中增强致瘤性。总体而言，IBC CSC 的多参数细胞生物物理表型和调节使人们对 IBC 的转移特性以及它们如何发展和成为治疗干预的目标有了新的认识。
Cancer stem-like cells (CSCs) have been shown to initiate tumorigenesis and cancer metastasis in many cancer types. Although identification of CSCs through specific marker expression helps define the CSC compartment, it does not directly provide information on how or why this cancer cell sub-population is more metastatic or tumorigenic. In this study, the functional and biophysical characteristics of aggressive and lethal inflammatory breast cancer (IBC) CSCs at the single-cell level are comprehensively profiled using multiple microengineered tools. Distinct functional (cell migration, growth, adhesion, invasion and self-renewal) and biophysical (cell deformability, adhesion strength and contractility) properties of ALDH+ SUM149 IBC CSCs are found as compared to their ALDH- non-CSC counterpart, providing biophysical insights into why CSCs has an enhanced propensity to metastasize. It is further shown that the cellular biophysical phenotype can predict and determine IBC cells' tumorigenic ability. SUM149 and SUM159 IBC cells selected and modulated through biophysical attributes-adhesion and stiffness-show characteristics of CSCs in vitro and enhance tumorigenicity in in vivo murine models of primary tumor growth. Overall, the multiparametric cellular biophysical phenotyping and modulation of IBC CSCs yields a new understanding of IBC's metastatic properties and how they might develop and be targeted for therapeutic interventions.