Discipline: Biological Sciences
Subcategory: Biomedical Engineering
Sydney M. Gibson - Rice University
Co-Author(s): Mary E. Dickinson, Baylor College of Medicine, Houston, TX
Cancer cells modulate their migration and metastatic activity in response to a tissue’s stromal microarchitecture. Although lung cancer accounts for the majority of cancer deaths worldwide, little focus has been placed on the effects of tissue stroma structure on lung cancer migration. Collagen hydrogels are commonly used as models to study stromal cancer cell migration in vitro. Despite collagen’s biomimetic properties, there is a need for a biomimetic model that allows for control of the matrix’s microstructure and pore size. We have developed a 3D in vitro model of lung cancer cell migration using laser micropatterned collagen hydrogels, which allows us to control the matrix pore size encountered by the tumor cells in the microenvironment. This model will allow us to identify the physical determinants of the matrix space that can enhance or impede lung tumor cell migration. Mouse lung adenocarcinoma tumor spheroids are embedded in a collagen I hydrogel. Confocal 2-photon laser scanning microscopy (2P-LSM) is used to laser-pattern 3D microtunnel voids into the gel defined by a user-created photomask. Microtunnels 5 – 20 μm in diameter are laser patterned adjacent to the spheroids. When microtunnels are ablated adjacent to tumor spheroids in 6 mg/mL gels, lung tumor cells are able to migrate into and expand tunnels as small as 5 μm in diameter within 24 hours. Tumor cells migrate collectively into the tunnels, maintaining cell-cell contact as they push against the matrix. These preliminary results suggest that lung adenocarcinoma cells primarily mechanically deform, rather than proteolytically remodel, the surrounding stroma as they invade. This also suggests that the architecture of the tumor stroma space can influence and guide lung cancer cell migration.
These initial results demonstrate how 2P-LSM patterning can generate microtunnels of defined geometries in a collagen hydrogel, allowing us to precisely manipulate the microarchitecture the cells experience. In the future, we can pattern tunnels of various sizes and geometries, and determine how the physical constraints of the microenvironment affect lung cancer cell invasion mechanisms. These results will lead to a better understanding of lung cancer metastasis into different tissues.
References: Sapudom, J., et al. Biomaterials 52 (2015): 367-375. Wolf, K., et al. Seminars in cell & developmental biology. Vol. 20. No. 8. Academic Press, 2009. Culver, J., et al. Advanced materials 24.17 (2012): 2344-2348.SGibson_ERN2016_Abstract.doc
Funder Acknowledgement(s): Cancer Prevention and Research Institute of Texas (CPRIT)
Faculty Advisor: Mary E. Dickinson, firstname.lastname@example.org