Biological Engineering Program, Utah State University, Logan, UT 84322-4105, USA.
Cancer Lett. 2010 Jul 1;293(1):82-91. doi: 10.1016/j.canlet.2009.12.016. Epub 2010 Jan 18.
Restoring BReast cancer Metastasis Suppressor 1 (BRMS1) expression suppresses metastasis in MDA-MB-435 human breast carcinoma cells at ectopic sites without affecting tumor formation at orthotopic site in the body. BRMS1 expression induces many phenotypic alterations in 435 cells such as cell adhesion, cytoskeleton rearrangement, and the down regulation of epidermal growth factor receptor (EGFR) expression. In order to better understand the role of cellular biomechanics in breast cancer metastasis, the qualitative and quantitative detection of cellular biomechanics and biochemical composition is urgently needed. In the present work, using atomic force microscopy (AFM) and fluorescent microscopy we revealed that BRMS1 expression in 435 cells induced reorganization of F-actin and caused alteration in cytoarchitectures (cell topography and ultrastructure). Results from AFM observed increase in biomechanical properties which include cell adhesion, cellular spring constant, and Young's modulus in 435/BRMS1 cells. Raman microspectroscopy showed weaker vibrational spectroscopic bands in 435/BRMS1 cells, implying decrease in concentration of cellular biochemical components in these cells. This was despite the similar spectral patterns observed between 435 and 435/BRMS1 cells. This work demonstrated the feasibility of applying AFM and Raman techniques for in situ measurements of the cellular biomechanics and biochemical components of breast carcinoma cells. It provides vital clues in understanding of the role of cellular biomechanics in cancer metastasis, and further the development of new techniques for early diagnosis of breast cancer.
恢复乳腺癌转移抑制因子 1（BRMS1）的表达可抑制 MDA-MB-435 人乳腺癌细胞在异位部位的转移，而不影响体内原位肿瘤的形成。BRMS1 的表达在 435 细胞中诱导许多表型改变，如细胞黏附、细胞骨架重排和表皮生长因子受体（EGFR）表达的下调。为了更好地理解细胞生物力学在乳腺癌转移中的作用，迫切需要对细胞生物力学和生化成分进行定性和定量检测。在本工作中，我们使用原子力显微镜（AFM）和荧光显微镜揭示了 BRMS1 在 435 细胞中的表达诱导了 F-肌动蛋白的重排，并导致细胞结构（细胞拓扑结构和超微结构）的改变。AFM 观察到的结果表明，BRMS1 表达增加了细胞黏附、细胞弹性常数和杨氏模量等生物力学特性。拉曼微光谱显示 435/BRMS1 细胞中的振动光谱带较弱，这意味着这些细胞中细胞生化成分的浓度降低。尽管在 435 和 435/BRMS1 细胞之间观察到相似的光谱模式，但仍存在这种情况。这项工作证明了应用 AFM 和 Raman 技术原位测量乳腺癌细胞的细胞生物力学和生化成分的可行性。它为理解细胞生物力学在癌症转移中的作用提供了重要线索，并进一步为乳腺癌的早期诊断开发了新技术。
