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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1802891
JournalSmall
DOIs
StateAccepted/In press - Jan 1 2019

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Inflammatory Breast Neoplasms
Neoplastic Stem Cells
Modulation
Bond strength (materials)
Formability
Tumors
Adhesion
Cells
Neoplasms
Growth
Cell Adhesion
Cell Movement
Carcinogenesis
Stem Cells
Neoplasm Metastasis
Phenotype

Keywords

  • biophysical property
  • cancer stem cells
  • inflammatory breast cancer

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

Cite this

Chen, W., Allen, S. G., Qian, W., Peng, Z., Han, S., Li, X., ... Fu, J. (Accepted/In press). Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem-Like Cells. Small, [1802891]. https://doi.org/10.1002/smll.201802891

Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem-Like Cells. / Chen, Weiqiang; Allen, Steven G.; Qian, Weiyi; Peng, Zifeng; Han, Shuo; Li, Xiang; Sun, Yubing; Fournier, Chelsea; Bao, Liwei; Lam, Raymond H.W.; Merajver, Sofia D.; Fu, Jianping.

In: Small, 01.01.2019.

Research output: Contribution to journalArticle

Chen, W, Allen, SG, Qian, W, Peng, Z, Han, S, Li, X, Sun, Y, Fournier, C, Bao, L, Lam, RHW, Merajver, SD & Fu, J 2019, 'Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem-Like Cells', Small. https://doi.org/10.1002/smll.201802891
Chen, Weiqiang ; Allen, Steven G. ; Qian, Weiyi ; Peng, Zifeng ; Han, Shuo ; Li, Xiang ; Sun, Yubing ; Fournier, Chelsea ; Bao, Liwei ; Lam, Raymond H.W. ; Merajver, Sofia D. ; Fu, Jianping. / Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem-Like Cells. In: Small. 2019.
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