The nanomechanical signature of breast cancer
The nanomechanical signature of breast cancer
复制标题
DOI：
10.1038/nnano.2012.167
复制
发表时间：
2012-11-01
影响因子：
38.3
通讯作者：
Schoenenberger, Cora-Ann
中科院分区：
文献类型：
--
作者：
Plodinec, Marija;Loparic, Marko;Schoenenberger, Cora-Ann
癌症的发生和发展遵循活组织的细胞外基质和细胞结构的复杂分子和结构变化。然而，它仍然知之甚少，从健康到恶性肿瘤的转变如何改变肿瘤微环境中细胞的机械特性。在这里，我们显示使用压痕型原子力显微镜（IT-AFM），纯人类乳腺活检显示不同的刚度配置文件。在正常和良性组织上获得的相关刚度图显示出以单个明显峰为特征的均匀刚度曲线。相反，恶性组织由于组织异质性而具有广泛的分布，具有代表癌细胞的突出的低刚度峰。在MMTV-PyMT转基因小鼠乳腺癌的特定阶段也观察到类似的发现。从患有晚期肿瘤的小鼠肺部获得的进一步证据表明，迁移和转移性扩散与缺氧相关癌细胞的低硬度相关。总的来说，IT-AFM的纳米力学分析提供了乳腺癌临床诊断中具有翻译意义的定量指标。
Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.