Automated Analysis of Extracellular Matrix Invasion of Cancer Cells from Tumor Spheroids

Abstract

The main cause of mortality among cancer patients is metastatic disease. Metastasis develops from cancer cells that invade the stromal tissue and intravasate the circulatory or lymphatic systems to eventually form new tumors in other organs. Blocking cancer cell invasion can potentially prevent or reduce the metastatic progression of cancers. Testing different chemical compounds against cell invasion in three-dimensional cultures is a common laboratory technique. The efficacy of the treatments is often evaluated from confocal microscopic images of the cells using image processing. However, the analysis approaches are often subject to variations and inconsistencies due to user decisions that must be made while processing each image. To overcome this limitation, we developed a fully automated method to quantify the invasion of cancer cells from a 3D tumor spheroid into the surrounding extracellular matrix. We demonstrated that this method resolves cell invasion from spheroids of different shapes and sizes and from cells that invade as a cluster or individually. We also showed that this approach can help quantify the dose-dependent anti-invasive effects of a commonly used chemotherapy drug. Our automated method significantly reduces the time and increases the consistency and accuracy of cancer cell invasion analysis in three-dimensional cultures.