Differential Contributions of Actin and Myosin to the Physical Phenotypes and Invasion of Pancreatic Cancer Cells.,Cellular and Molecular Bioengineering

当前位置： X-MOL 学术 › Cel. Mol. Bioeng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Differential Contributions of Actin and Myosin to the Physical Phenotypes and Invasion of Pancreatic Cancer Cells.
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2019-10-31 , DOI: 10.1007/s12195-019-00603-1
Angelyn V Nguyen ₁ , Brittany Trompetto ₁ , Xing Haw Marvin Tan ₂ , Michael B Scott _{1,

3,

4,

5} , Kenneth Hsueh-Heng Hu ₆ , Eric Deeds _{1,

7} , Manish J Butte _{8,

9} , Pei Yu Chiou _{2,

3} , Amy C Rowat _{1,

2,

10}

Affiliation

Department of Integrative Biology and Physiology, University of California, 610 Charles E Young Dr. East, Los Angeles, CA 90095 USA.
Department of Bioengineering, University of California, Los Angeles, USA.
Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, USA.
Present Address: Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, USA.
Department of Biomedical Engineering, Northwestern McCormick School of Engineering, Evanston, USA.
Stanford Biophysics, Stanford University, Stanford, USA.
Institute for Quantitative and Computational Biology, University of California, Los Angeles, USA.
Department of Pediatrics, University of California, Los Angeles, USA.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, USA.
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, USA.

Introduction

Metastasis is a fundamentally physical process in which cells deform through narrow gaps and generate forces to invade surrounding tissues. While it is commonly thought that increased cell deformability is an advantage for invading cells, we previously found that more invasive pancreatic ductal adenocarcinoma (PDAC) cells are stiffer than less invasive PDAC cells. Here we investigate potential mechanisms of the simultaneous increase in PDAC cell stiffness and invasion, focusing on the contributions of myosin II, Arp2/3, and formins.

Method

We measure cell invasion using a 3D scratch wound invasion assay and cell stiffness using atomic force microscopy (AFM). To determine the effects of actin- and myosin-mediated force generation on cell stiffness and invasion, we treat cells with pharmacologic inhibitors of myosin II (blebbistatin), Arp2/3 (CK-666), and formins (SMIFH2).

Results

We find that the activity of myosin II, Arp2/3, and formins all contribute to the stiffness of PDAC cells. Interestingly, we find that the invasion of PDAC cell lines is differentially affected when the activity of myosin II, Arp2/3, or formins is inhibited, suggesting that despite having similar tissue origins, different PDAC cell lines may rely on different mechanisms for invasion.

Conclusions

These findings deepen our knowledge of the factors that regulate cancer cell mechanotype and invasion, and incite further studies to develop therapeutics that target multiple mechanisms of invasion for improved clinical benefit.

中文翻译：

肌动蛋白和肌球蛋白对胰腺癌细胞的物理表型和侵袭的不同贡献。

介绍

转移是一个基本的物理过程，其中细胞通过狭窄的间隙变形并产生侵入周围组织的力。虽然人们普遍认为细胞变形能力的增加对于侵袭细胞来说是一个优势，但我们之前发现侵袭性更强的胰腺导管腺癌细胞 (PDAC) 比侵袭性较小的 PDAC 细胞更硬。在这里，我们研究了 PDAC 细胞硬度和侵袭同时增加的潜在机制，重点关注肌球蛋白 II、Arp2/3 和福明斯的贡献。