Cellular Traction Force Holds the Potential as a Drug Testing Readout for In Vitro Cancer Metastasis

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2024-07-04 DOI:10.1007/s12195-024-00811-4

Hui Yan Liew, Xiao Hui Liew, Wei Xuan Lin, Yee Zhen Lee, Yong Sze Ong, Satoshi Ogawa, Lor Huai Chong

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Abstract

Introduction

Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis.

Methods

In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis.

Results

MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models.

Conclusion

Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.

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细胞牵引力有望成为体外癌症转移的药物测试读数

导言：全球 90% 的癌症相关死亡病例都是转移造成的。然而，各种抗癌药物对转移瘤的潜在抑制作用在很大程度上尚未得到研究。现有的临床前模型主要关注原发肿瘤的抗增殖药物，以阻止癌症生长，但对转移瘤却没有作用。与原发肿瘤不同，转移瘤需要癌细胞通过肌动蛋白机制产生足够的细胞牵引力，以远离原发肿瘤部位。因此，我们试图探索细胞牵引力作为一种新型读数的潜力，以筛选针对癌症转移的药物。方法首先分别使用 MDA-MB-231 和 MCF-7 细胞系建立了浸润性和非浸润性乳腺癌的体外模型。对细胞形态进行表征，发现 MDA-MB-231 细胞呈纺锤形，MCF-7 细胞呈球形。使用牵引力显微镜技术对基线细胞牵引力进行了量化。结果MDA-MB-231细胞的基线细胞牵引力明显高于MCF-7细胞。抗转移药物顺铂和非抗转移药物 5-氟尿嘧啶 (5FU) 对 MDA-MB-231 细胞的细胞牵引力有不同的影响，但对 MCF-7 细胞没有影响。这些发现与在这两种模型中观察到的侵袭潜力相关。这种方法可以促进新型抗转移疗法的筛选和开发，解决目前抗癌药物研究中的一个关键缺口。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.