Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem-Like Cells

Weiqiang Chen; Steven G Allen; Weiyi Qian; Zifeng Peng; Shuo Han; Xiang Li; Yubing Sun; Chelsea Fournier; Liwei Bao; Raymond H W Lam; Sofia D Merajver; Jianping Fu

doi:10.1002/smll.201802891

Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem-Like Cells

Small. 2019 Feb;15(5):e1802891. doi: 10.1002/smll.201802891. Epub 2019 Jan 11.

Authors

Weiqiang Chen^{1

2}, Steven G Allen³, Weiyi Qian¹, Zifeng Peng⁴, Shuo Han⁴, Xiang Li⁴, Yubing Sun⁵, Chelsea Fournier⁶, Liwei Bao⁷, Raymond H W Lam⁸, Sofia D Merajver^{3

7}, Jianping Fu^{4

9}

Affiliations

¹ Department of Mechanical and Aerospace Engineering, New York University, Brooklyn, NY, 11201, USA.
² Department of Biomedical Engineering, New York University, Brooklyn, NY, 11201, USA.
³ Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵ Mechanical and Industrial Engineering, University of Massachusetts, Amherst, MA, 01003, USA.
⁶ Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI, 48109, USA.
⁷ Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
⁸ Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
⁹ Department of Biomedical Engineering, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.

Abstract

Cancer stem-like cells (CSCs) have been shown to initiate tumorigenesis and cancer metastasis in many cancer types. Although identification of CSCs through specific marker expression helps define the CSC compartment, it does not directly provide information on how or why this cancer cell subpopulation is more metastatic or tumorigenic. In this study, the functional and biophysical characteristics of aggressive and lethal inflammatory breast cancer (IBC) CSCs at the single-cell level are comprehensively profiled using multiple microengineered tools. Distinct functional (cell migration, growth, adhesion, invasion and self-renewal) and biophysical (cell deformability, adhesion strength and contractility) properties of ALDH+ SUM149 IBC CSCs are found as compared to their ALDH- non-CSC counterpart, providing biophysical insights into why CSCs has an enhanced propensity to metastasize. It is further shown that the cellular biophysical phenotype can predict and determine IBC cells' tumorigenic ability. SUM149 and SUM159 IBC cells selected and modulated through biophysical attributes-adhesion and stiffness-show characteristics of CSCs in vitro and enhance tumorigenicity in in vivo murine models of primary tumor growth. Overall, the multiparametric cellular biophysical phenotyping and modulation of IBC CSCs yields a new understanding of IBC's metastatic properties and how they might develop and be targeted for therapeutic interventions.

Keywords: biophysical property; cancer stem cells; inflammatory breast cancer.

Publication types

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

MeSH terms

Aldehyde Dehydrogenase / metabolism*
Biomechanical Phenomena
Biophysics*
Carcinogenesis / metabolism
Carcinogenesis / pathology
Cell Adhesion
Cell Line, Tumor
Female
Humans
Inflammatory Breast Neoplasms / enzymology*
Inflammatory Breast Neoplasms / pathology*
Neoplastic Stem Cells / enzymology*
Neoplastic Stem Cells / pathology*
Phenotype

Substances

Aldehyde Dehydrogenase

Abstract

Publication types

MeSH terms

Substances

Grants and funding