Extracellular matrix (ECM) is a complex mixture of structural proteins which provide essential physical scaffolds to maintain tissue structure and modulate cellular function such as differentiation, migration, proliferation, and survival. In many epithelial cancers (lung, colon, breast, pancreas and many others), loss of stability in the normal stroma due to series of tumor associated changes results in chronic inflammation. These inflammatory stresses support mechanical and biochemical changes that result in the formation of an activated/pathological fibrotic stroma, known as “desmoplasia.” Desmoplasia bearing epithelial cancers comprise ECM characteristic that has been shown to correlate with poor patient survival, yet the particular tumor promoting mechanisms that are associated with desmoplasia remain unclear. Therefore, to accurately study tumor associated desmoplasia, there is a need to develop 3D ECM systems which closely relate to what cells experience in vivo.
Summary of the Invention
Cancer associated fibroblasts (CAFs) are the main producers of desmoplastic stromal ECM. Previously reported CAF-derived ECM have a significant limitation since the matrix is deposited on plastic or glass surfaces that may lead to inaccuracy of interpretation of data. Researchers from Fox Chase Cancer Center have developed a novel 3D cell-derived extracellular matrix/gel system that overcome the previously existing limitations and can accurately mimic the natural stromal environment and incorporate the stromal dynamic changes that are seen in vivo. In their approach, fibroblasts are cultured on top of inert Collagen-I conjugated 2D polyacrylamide gels that bear stiffness ranges of physiological versus cancerous tissue. This novel 3D ECM/gel system offers advantage that cells can now sense stiffness of their “natural” tissue environment and while the system maintains in vivo biochemical complexicity and spatial organization of extracellular matrix scaffolds 3D topography.
The newly generated 3D ECM/gel system provides a more physiologically relevant approach to study tumor promoting mechanisms, discover potential new targets and design new therapies (drug screenings for anti-cancer or anti-fibrotic activity).
Patent Status: A Provisional Application has been filed
For Licensing/Partnering information, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer