Tissue Engineering: Tumor Engineering
Hyaluronic acid (HA) is enriched in tumors or the stroma surrounding the tumors. Interactions between HA and its receptors (CD44 and RHAMM) increase the invasive potential by binding with bone marrow endothelial cells and facilitating intravasation into the new tumor site. We hypothesize that HA-baed 3D hydrogel matrices will provide biomimetic microenvironments for the growth of cancer cells. Fundamental studies using these matrices will not only improve our understanding in basic cancer cell biology but also lead to improved methods for the prevention and treatment of the disease.
In the current study, C4-2B cells of the LNCaP line were encapsulated in HAALD/HAADH gels in situ. The cell-laden matrices were incubated for one week with or without added anticancer drugs. Cells cultured in the HA gels showed a higher apoptosis response than did those on plastic, possibly due to more natural cell morphology, 3D cell-cell contact as well as the altered gene expression and signaling. The HA hydrogel system provides a useful new alternative to study anti-neoplastics on poorly adherent cell types such as those which have metastasized to the bone marrow and have the potential to expand the list of prostate cancer cells for high-throughput testing.
1. Gurski, L. A.; Petrelli, N. J.; Jia, X.; Farach-Carson, M. C. "Three-Dimensional Matrices for Anti-Cancer Drug Testing and Development" Oncology Issues, 2010, 25, 20-25.
2. 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.