MATRIX-ATTACHMENT THERAPY: A STRATEGY TO DELIVER 5-FLUOROURACIL TO TUMOR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hyaluronan (HA) is a ubiquitous glycosaminoglycan found in all tissues and body fluids of vertebrates. The basal levels of HA is low in normal tissues, but elevated levels of HA are found in various malignant tumors, including melanoma, ovaries, breast, glioblastoma, and bladder cancer cells. The CD44 macromolecule is a membrane protein that can bind to hyaluronan via its extraceullar domain. We are creating a fusion protein between the extracellular domain of CD44 and cytosine deaminase. Our hypothesis is that the fusion protein will bind to HA in the extracellular matrix and covert the orally available 5-fluorocytosine to 5-fluorouracil. We believe this will create a chemotherapeutic fence around the tumor and improve antitumor therapy. Currently, we use various sequence analysis tools that are available from the Computer Graphics Laboratory and we plan to use Chimera to visualize the structures of functional domains for modified fusion proteins.