Abstract 33: Characterizing the Changes in Mechanical Properties of the Actin Cortex in Highly Metastatic Cancers

Abstract

Abstract Purpose: Cancer is the second leading cause of death globally with approximately 9.5 million cancer related deaths worldwide in 2018. Many of these deaths are the result of complications due to metastatic progression. Metastasis is a complex, dynamic process that requires cancerous cells to undergo major cytoskeletal reorganization prior to migration and intravasation. Previous research studying the biophysical properties of the cytoskeleton utilize techniques that require the cells be adhered to a hard substrate, causing modifications to the organization of the cytoskeleton that are not physiologically relevant. To better understand the mechanics of cancer cells and metastasis, we have developed an alternative approach to studying the cell cortex. Methods: Utilizing a novel, Atomic Force Microscopy-based, quasi-static force spectroscopy method pioneered by our lab, we are able to measure cortical tension and intracellular pressure by gently compressing non-adherent cells with a tipless cantilever, which results in a more physiologically relevant cortical morphology. We utilized this method to compare changes in cortical mechanics between healthy and cancerous cells, as well during metastatic progression of cancer cells in vitro for melanoma, breast, and ovarian cancers. Results: Previous research that utilized adherent cells indicated a decrease in stiffness after tumorigenesis, but our method indicates an increase in stiffness by determining the cortical tension and intracellular pressure in the case of melanoma. Additionally, a non-linear, overall decrease in tension and pressure can be seen in both the melanoma and ovarian cell lines that model increasing metastatic potential. Conclusion: Due to the important role invasiveness plays in the severity of cancer, categorizing the mechanical properties of cancer cells may prove to be a critical diagnostic and prognostic indicator for oncologists. Our novel force microscopy method better captures physiologically relevant cortical morphology and may enable the capture of clinically significant information on tumor invasiveness and progression. Citation Format: Jamie Neal, Chynna Smith, Michelle Baird, Alexander Cartagena-Rivera. Characterizing the Changes in Mechanical Properties of the Actin Cortex in Highly Metastatic Cancers [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 33.