Frederic A. Troy II, professor and chair emeritus of biochemistry and molecular medicine, has received a globally competitive research grant from the Mizutani Foundation for Glycoscience to better understand structural changes associated with metastasis of adult cancer cells and stem cells.
Troy’s study, titled “Functional Analyses of Polysialic Acid DP on Human Cancer and Stem Cells,” specifically focuses a compound found in neural cell adhesion molecules that can regulate the cell-to-cell adhesive processes on human cancer and stem cells. His laboratory will investigate the degree of polymerization of polysialic acid and its role in activating key cancer signaling pathways.
“A key question that remains unresolved in cancer, glyco-neurobiology and stem cell biology is how can the polysialic acid (polySia) glycotope on neural cell adhesion molecules modulate such a variety of functions in the developing nervous and immune system?” said Troy, one of the first faculty members hired by Nobel Prize winner Edwin G. Krebs when Krebs chaired the biological chemistry department at UC Davis School of Medicine in 1968. “These functions include cell migration, cell contact dependent differentiation, tumor metastasis, neural stem cell proliferation and differentiation, immune response, cell signaling and cytokine response, axon path finding, synaptogenesis, neural plasticity and cognition and memory.”
PolySia is an oncodevelopmental tumor-associated surface antigen that can be re-expressed on the surface of adult cancer cells. When this re-expression occurs, polySia becomes a metastatic factor that promotes tumor-cell detachment, invasion and colonization at distant sites. This fundamental event is a key molecular determinant in allowing polysialylated human cancer cells to detach and spread or metastasize throughout the body, a hallmark of malignancy.
The polySia glycotope modulates neuronal development. It is also expressed on human hematopoietic stem cells and regulates immune responses. In this case, the DP of polySia on human NK cells is responsive to their activation state.
“The Mizutani Glycoscience grant will allow us to test the hypothesis that the degree of polymerization of polySia chains on neural cell adhesion molecules is a critically important structural and conformational feature in regulating the myriad of cell adhesive and cell migration processes,” said Troy. “Such studies have not been previously reported.”
Troy is also a member of the UC Davis Comprehensive Cancer Center and the UC San Diego Glycobiology Training Center. He is past president of the professional Society for Glycobiology and an internationally renowned expert in the field of glycochemistry.
The Mizutani Foundation is a nonprofit organization established in 1992 to advance studies in the field of glycoscience, especially glycoconjugates, important compounds involved in cell-to-cell communications, from recognition to detoxification processes.