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

Abstract

e15526 Background: Even years after successful treatment of the primary tumor about 30% of breast cancer patients are suffering from metastatic relapse. One reason might be hematogenous spread. Therefore circulating tumor cells (CTC) in the blood might be interesting and easy accessible surrogate markers for disease monitoring. Due to phenotypical, mechanical and functional changes during cancer progression and treatment response, isolation of CTC subpopulations remains very challenging. Here we focused on the characterization of CTC mechanics to evaluate the utility of mechanical parameters for CTC separation from blood. Methods: For the first time, we investigated the active and passive mechanical CTC properties such as elasticity, viscosity and contractile force exertion using a dual beam trap. For proof of premise we used peripheral blood mononuclear cells (PBMC) from a healthy donor and human GFP-expressing MDA-MB 231 breast cancer cells to mimic a CTC model system and to measure cell type specific mechanical deformation profiles using an optical rheometer. For translational experiments blood samples were collected from patients with mamma or vulvar carcinoma. Hematopoietic cells were depleted using CD45. The remaining cell suspensions were applied to the optical stretcher and rheological parameters were measured in the same manner. Results: We were able to reveal distinct mechanical profiles from hematopoietic cells and breast cancer cells, respectively. The optical deformability was significantly different in both the model and the translational, systems comparing healthy PPMC to MDA-MB 231 cells, respective possible CTC candidates from breast and vulvar carcinoma patients. Evaluation of secondary parameters like viscosity and activity using a machine learning algorithm allowed for a clear distinction between hematopoietic and cancer cells in the model system. CD45-positive and -negative cells from patients with mamma or vulvar carcinoma (n = 7) showed distinct differences in the rheological behavior of both cell populations. Surprisingly, the mechanical profiles of CD45-negative cells from mamma carcinoma samples were severely different from vulvar carcinoma. Conclusions: Together with morphology and cell size, the cellular deformation pattern might be a proper tool for marker-free CTC detection in the peripheral blood of breast cancer patients.