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

Abstract

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.

Recent advances of liquid biopsy: Interdisciplinary strategies toward clinical decision‐making

“…As a result, CTCs offer tremendous potential by providing comprehensive and dynamic information about cancers through the analysis of easily accessible body fluids to improve cancer diagnostics, treatment monitoring, and personalized therapies. 7,19,20 EVs are small vesicles surrounded by a lipid-bilayer membrane that are derived from various types of cells, 11,21 which are produced by outward budding and fission, cell fusion, or cell apoptosis. 22 They play a crucial role in intercellular communication, facilitating processes such as membrane remodeling, removal of cellular component.…”

“…Furthermore, CTCs carry the complete information of the tumor tissue, including its genome, transcriptome, proteome, and metabolome. As a result, CTCs offer tremendous potential by providing comprehensive and dynamic information about cancers through the analysis of easily accessible body fluids to improve cancer diagnostics, treatment monitoring, and personalized therapies 7,19,20 . EVs are small vesicles surrounded by a lipid‐bilayer membrane that are derived from various types of cells, 11,21 which are produced by outward budding and fission, cell fusion, or cell apoptosis 22 .…”

Label-free detection and enumeration of rare circulating tumor cells by bright-field image cytometry and multi-frame image correlation analysis

“…These technologies were mainly based on the cells' inherent properties ( e.g. , cell size, 12–15 mechanical characteristics, 16,17 or electric charges 18 ) and took advantage of the well-established systems ( e.g. , mass spectrometry, 19,20 Raman scattering, 21–23 electrochemical analysis 24,25 and morphological image analysis 26 ).…”

Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications

“…It is the dynamic ability of being able to deform and simultaneously resist deformation that allows tumor cells to undergo the metastatic cascade. Therefore, a method to prevent metastasis for solid tumors would be to stiffen and decrease the cell shape change ability (8,13,(23)(24)(25)(26)(27).…”