Migration and Mechanical Invasiveness in Breast Cancer Cells, are they Related?

Tumor cell migration and invasion are critical steps in metastasis, and their study has provided many targets for cancer therapy. Different transmigration assays have been designed to evaluate invasiveness of cancer cells through their ability to cross small pores in, such as Boyden chambers. Previously, we have used mechanical interactions, or forces applied by cells distinguish between benign and breast cancer cells with different metastatic potential (MP). Specifically, we measure the normal forces applied by breast cancer cell lines on a soft, impenetrable, polyacrylamide gel-substrate, resulting in gel-indentation during attempted cell penetration; about 50% of cancer cells indented gels, while no benign cells indent. Here, we correlate the populations of cells that are able to transmigrate through a Boyden chamber with those that apply normal forces and indent gels, to show a correlation between transmigration and mechanical invasiveness. When high MP cells are seeded on the gel 50% will indent. However, we have found that 45% of high MP cells transmigrate through a Boyden chamber (8µm pore size), and if that population is seeded on the gel, 70% of cells indent the gels. Thus the Boyden chamber effectively “concentrates” the more invasive cell population. Furthermore, our results show that migration and mechanical invasiveness are directly correlated in breast cancer cells. Most importantly, our results validate the gel-based assay for mechanical interactions as an invasiveness assay and in contrast to Boyden chamber, our assay provides quantitative measurements (e.g. normal force, indentation depth) to evaluate invasiveness.