Probing the Biophysical Properties of Primary Breast Tumor-Derived Fibroblasts

Turi A. Alcoser, Francois Bordeleau, Shawn P. Carey, Marsha C. Lampi, Daniel R. Kowal, Sahana Somasegar, Sonal Varma, Sandra J. Shin, Cynthia A. Reinhart-King

As cancer progresses, cells must adapt to a new and stiffer environment, which can ultimately alter how normal cells within the tumor behave. In turn, these cells are known to further aid tumor progression. Therefore, there is potentially a unique avenue to better understand metastatic potential through single-cell biophysical assays performed on patient-derived cells. Here, we perform biophysical characterization of primary human fibroblastic cells obtained from mammary carcinoma and normal contralateral tissue. Through a series of tissue dissociation, differential centrifugation and trypsinization steps, we isolate an adherent fibroblastic population viable for biomechanical testing. 2D TFM and 3D migration measurements in a collagen matrix show that fibroblasts obtained from patient tumors generate more traction forces and display improved migration potential than their counterparts from normal tissue. Moreover, through the use of an embedded spheroid model, we confirmed the extracellular matrix (ECM) remodeling behavior of primary cells isolated from carcinoma. Overall, correlating biophysical characterization of normal- and carcinoma-derived samples from individual patient along with patient outcome may become a powerful approach to further our comprehension of metastasis and ultimately design drug targets on a patient-specific basis.