Tissue Engineering: Tumor Engineering

Cancer progression and metastasis depends on the dynamic and intricate interactions between cancer cells and their surrounding microenvironment. Such interactions can be of biochemical nature, through growth factor–mediated tumor–stromal cell crosstalk and integrin–mediated tumor–matrix interactions, or of biomechanical origin, through the exchange of physical forces to enable cell migration through the dense ECM network to establish secondary tumors. We have developed biologically–relevant hydrogel culture systems that recapture essential features of prostate cancer (PCa) and its associated stroma. We discovered that PCa cells entrapped in chemically defined hyaluronic acid (HA) matrices formed distinct multicellular aggregates, expressed pro–angiogenic factors and up–regulated the production of drug resistant proteins. The PCa model was used successfully to test the efficacy of anti–cancer drugs, free or encapsulated in polymeric nanoparticles. We are currently exploring the utility of bio–orthogonally constructed synthetic matrices for the engineering of advanced, metastatic PCa models. Parallel work is under way to integrate photonic sensor arrays for real time mapping of cellular forces as PCa cells grow, expand and migrate in synthetic matrices.

Collaborators:

• Kenneth Pienta: Brady Urological Institute, Johns Hopkins School of Medicine

Selected Publications

1. Hao, Y.; Zerdoum, A. B.; Stuffer, A. J.; Rajasekaran, A. K; Jia, X.* "Biomimetic Hydrogels Incorporating Polymeric Cell–Adhesive Peptide to Promote the 3D Assembly of Tumoroids", Biomacromolecules, 2016, 17, 3750"3760. Link.
2. Xu, X.; Farach–Carson, M. C.; Jia, X.* "Three–Dimensional In Vitro Tumor Models for Cancer Research and Drug Evaluation", Biotechnol Adv, 2014, 32, 1256–1268. Link.
3. Xu, X.; Sabanayagam, C. R.; Harrington, D. A.; Farach–Carson, M. C.; Jia, X.* "A Hydrogel–Based Tumor Model for the Evaluation of Nanoparticle–Based Cancer Therapeutics" Biomaterials, 2014, 35, 3319–3330.
4. 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.
5. 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.
6. 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.