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Article

The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

1
Department of Gynecology, Medical Center, University of Leipzig, 04103 Leipzig, Germany
2
Soft Matter Physics Division, Peter-Debye-Institute Leipzig, University of Leipzig, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this paper.
Academic Editor: David Brindley
Cancers 2021, 13(5), 1119; https://doi.org/10.3390/cancers13051119
Received: 22 January 2021 / Revised: 17 February 2021 / Accepted: 26 February 2021 / Published: 5 March 2021
(This article belongs to the Special Issue Tumor Heterogeneity: Recent Trends and Current Issues)
Detection of circulating tumor cells (CTCs) in the blood of cancer patients is a challenging issue, since they adapt to the biochemical and physical landscape of the bloodstream. We approached the issue of CTC identification on a biophysical level. For the first time, we recorded the mechanical deformation profiles of potential CTCs, which were isolated from the blood of breast cancer patients, at the force regime of the deforming blood flow. Mechanical fingerprints of CTCs were significantly different from healthy white blood cells. We used machine learning to further evaluate the differences and identify discrimination criteria. Our results suggest that mechanical characterization of CTCs at low forces is a promising path towards CTC detection.
Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection. View Full-Text
Keywords: circulating tumor cells; CTCs; optical stretcher; cell mechanics; breast cancer circulating tumor cells; CTCs; optical stretcher; cell mechanics; breast cancer
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MDPI and ACS Style

Nel, I.; Morawetz, E.W.; Tschodu, D.; Käs, J.A.; Aktas, B. The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients. Cancers 2021, 13, 1119. https://doi.org/10.3390/cancers13051119

AMA Style

Nel I, Morawetz EW, Tschodu D, Käs JA, Aktas B. The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients. Cancers. 2021; 13(5):1119. https://doi.org/10.3390/cancers13051119

Chicago/Turabian Style

Nel, Ivonne, Erik W. Morawetz, Dimitrij Tschodu, Josef A. Käs, and Bahriye Aktas. 2021. "The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients" Cancers 13, no. 5: 1119. https://doi.org/10.3390/cancers13051119

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