Year: 2019
Type: article
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.
Source: Small
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Science Foundation, Avon Foundation for Women, American Heart Association, Breast Cancer Research Foundation, University of Michigan, National Institutes of Health, Michigan Institute for Clinical and Health Research, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, Division of Electrical, Communications and Cyber Systems, National Center for Advancing Translational Sciences
Awards: G1083174490, Nanotopography-dependent neural induction of human induced pluripotent stem cells for post stroke neural rehabilitation, G293065720, Engineered Glioblastoma Tumor Immunity for Personalized Immunotherapy, G4214190409, SPORE in Prostate Cancer, Michigan Institute for Clinical and Health Research (MCHR), Michigan Institute for Clinical and Health Research (MICHR), Molecular Sieving in Two-Dimensional Periodic Free-Energy Landscapes Created by Patterned Nanofluidic Devices, Interleukin-4 Drives Tumor-Associated Macrophage Polarization to Promote Tumor Gr, G9000105751
OpenAlex ID: W2908871841