A Novel Way to Characterize the Non-Specific Surface Adhesion of Cancer Cells and Understand Cancer Metastasis

Abstract

Cancer deaths are mostly caused by the metastasis of the malignant cells, not by the primary tumor itself. During metastasis, cancer cells detach from the primary tumor, spread to different tissues via blood circulation or lymph system, and reattach to invade new tissues and organs. In this project, we hypothesize that cancer cells manage their invasion by changing their surface adhesivity. To study the cell surface adhesivity, a novel and versatile microelectromechanical systems (MEMS) force sensor is developed to quantify the strength of adhesion between living cancer cells and a probe. The Silicon sensors consist of a probe and 2 flexible cantilever beams, while the probe is used to contact the cancer cell and the flexible beams are used to measure the cell force response in the range from nN to uN. The spring constant of the sensor is 14 nN/ μm. Our results demonstrate that the aggressive HCT-8 cells (from human colon adenocarcinoma) show high nonspecific adhesivity when they aggregate into cell islands, and low surface non-specific adhesivity after they disassociate from the cell islands. The surface adhesivity of less aggressive Caco-2 cells (from human colon carcinoma) and normal MA104 cell (from monkey kidney) are found to be lower than that of before-disassociation HCT-8 cells. Furthermore, the adhesion force response of cancer cells is found to show 2-slope force behavior, which is different from previous results of focal-adhesion detachment experiments. The 2-stage force bearing model is proposed to interpret the underlying mechanism.