Cancer cells display increased migration and deformability in pace with metastatic progression

Zhenhui Liu; Se Jong Lee; Seungman Park; Konstantinos Konstantopoulos; Kristine Glunde; Yun Chen; Ishan Barman

doi:10.1096/fj.202000101RR

Cancer cells display increased migration and deformability in pace with metastatic progression

FASEB J. 2020 Jul;34(7):9307-9315. doi: 10.1096/fj.202000101RR. Epub 2020 May 28.

Authors

Zhenhui Liu¹, Se Jong Lee², Seungman Park^{1

3

4}, Konstantinos Konstantopoulos^{2

3

5

6

7}, Kristine Glunde^{8

9}, Yun Chen^{1

3

4}, Ishan Barman^{1

7

8}

Affiliations

¹ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
² Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
⁴ Center for Cell Dynamics, Johns Hopkins University, Baltimore, MD, USA.
⁵ Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD, USA.
⁶ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
⁸ The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

In this study, we explored the relation between metastatic states vs the capacity of confined migration, amoeboid transition, and cellular stiffness. We compared across an isogenic panel of human breast cancer cells derived from MDA-MB-231 cells. It was observed that cells after lung metastasis have the fastest migration and lowest stiffness, with a significantly higher capacity to transition into an amoeboid mode. Our findings illustrate that metastasis is a selective process favoring motile and softer cells. Moreover, the observation that circulating tumor cells resemble the parental cell line, but not lung-metastatic cells, suggests that cells with higher deformability and motility are likely selected during extravasation and colonization.

Keywords: amoeboid movement; breast cancer metastasis; isogenic cell lines; mechanotyping; microchannel migration.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Breast Neoplasms / pathology*
Cell Movement*
Cell Proliferation
Disease Progression
Epithelial-Mesenchymal Transition*
Female
Humans
Lung Neoplasms / secondary*
Neoplasm Metastasis
Tumor Cells, Cultured

Abstract

Publication types

MeSH terms

Grants and funding