Tissue Engineering: Tumor Engineering
An early event in carcinogenesis is loss of polarity and detachment from the natural basement membrane, allowing cells to form distinct 3D structures that interact with each other and with the surrounding microenvironment. The traditional 2D culture condition does not reflect many of the essential properties of the tumor tissue. This shortcoming, along with lack of depth and cell connectivity, limits their ability to serve as perfect models for testing of pharmacologically active compounds. Further, the most detrimental aspect of cancer is its invasiveness. A fundamental understanding of cancer metastasis cannot be readily obtained from 2D cell culture studies. Thus, there is a critical need to develop 3D matrices that closely mimic the natural microenvironment of tumor tissues for evaluating anticancer drugs and assessing cancer metastasis.
In collaboration with Prof. Mary C. Farach–Carson, we have developed a hyaluronic acid (HA)–based, in situ
crosslinkable hydrogel system to encapsulate living cancer cells. We have demonstrated that this system maintains cell growth and viability, and that cancer cells within the HA hydrogel form distinct aggregated structures reminiscent of real tumors. The HA hydrogel system was used to test the efficacy of several anti–cancer drugs including specificity, dose and time responses, alone and in combination. Responses of cells to anti–neoplastics differed between the 3D HA hydrogel and 2D monolayer systems. Current effort is dedicated to the understanding of cancer invasion and metathesis using HA hydrogels incorporating chemo–attractant releasing HA hydrogel particles. The engineered tumor model is also being used to test the efficacy of the cancer drug delivery systems that have been developed in my laboratory.
- Mary C. Farach–Carson, Department of Biochemistry and Cell Biology, Rice University
- Gurski, L. A.; Xu, X.; Labrada, L. N.; Nguyen, N. T.; Xiao, L.; van Golen, K. L.; Jia, X.; Farach–Carson, M. C.* "Hyaluronan (HA) Interacting Proteins RHAMM and Hyaluronidase Impact Prostate Cancer Cell Behavior and Invadopodia Formation in 3D HA–Based Hydrogels", PLoS One, 2012, 7, e50075.
- Xu, X.; Gurski, L. A.; Zhang, C.; Harrington, D. A.; Farach–Carson, M. C.; Jia, X.* "Recreating the Tumor Microenvironment in a Bilayer, Hyaluronic Acid Hydrogel Construct for the Growth of Prostate Cancer Spheroids", Biomaterials, 2012, 33, 9049–9060.
- Gurski, L. A.; Jha, A. K.; Zhang, C.; Jia, X.; Farach–Carson, M. C.* "Hyaluronic Acid Hydrogel as 3D Matrices for in vitro Evaluation of Chemotherapeutic Drugs Using Poorly Adherent Cells" Biomaterials, 2009, 30, 6076–6085.