Can breast cancer cells be distinguished from blood cells by mechanical parameters? A label-free CTC detection approach

Background:

Even years after successful treatment of the primary tumor about one third of breast cancer patients are suffering from metastatic relapse. One reason might be hematogenous spread during early disease stages when isolated tumor cells change their physical properties from epithelial to mesenchymal features (EMT) and become able to disseminate from the primary tumor site. Therefore circulating tumor cells (CTCs) might be interesting and easy accessible surrogate markers to monitor disease progression and treatment response in the clinical setting.

Methodology and Results:

One promising CTC detection approach could be based on mechanical properties such as deformability using an optical rheometer. PBMC were isolated from the peripheral blood of a healthy donor using density gradient centrifugation. Breast cancer cells MDA-MB 231 were cultured under standard conditions. Both cell suspensions were applied separately to the optical stretcher and rheological parameters such as deformability and stiffness were measured. Distinct cellular profiles could be obtained from hematopoetic cells and breast cancer cells, respectively. Relative deformation was significantly different between both cell types. Furthermore, 10:1 mixtures of PBMC and MDA-MB 231 cells were analyzed with the optical stretcher. Results indicated that the mixed samples could be sorted into subpopulations of significantly different cellular stiffness based on mechanical parameters such as cell size.

Conclusions and Outlook:

Once significant differences between cellular profiles of the mixed samples with low numbers of spiked tumor cells can be measured, the methodology might be transferred to clinical samples in order to develop a liquid biopsy test.