Abstract
Invasion of cells plays a major role in metastasis. Cancer cells interact with cancer-associated fibroblasts (CAFs) present in the tumor microenvironment and as a result enhance their invasive ability. However, the overall mechanism of the interaction has not been clarified. When cancer cells moving, they constantly exert power on the surrounding extracellular matrix (ECM). In addition, the material properties of the ECM are not uniform because the fiber structure constantly changes. Therefore, measuring the mechanical field around cancer cells is significant in revealing the interaction between cancer cells and CAFs. In this study, we analyze what kind of change is caused in the mechanical field of ECM around a cancer cell by the effects of CAFs under three dimensional culture. We cultured the pancreatic ductal carcinoma cells, SUIT-2 with the orthotopic CAFs in collagen gel. Three-dimensional images were acquired by a confocal microscope. Embedding the fluorescent beads in the gel at the same time, the beads adhere to the collagen and form a pattern, therefore it is possible to track the displacement field by using the digital volume correlation (DVC) method. At the same time, the collagen fiber density and orientation were evaluated based on 3D images. As a result, accumulation and arrangement of collagen fibers were observed in the direction of CAF protrusion, and it became clear that cancer cells under the influence of CAFs generate a dynamic field in a wider range.
