Grant: Project Grant

Many proteins expressed by cancer cells are modified with carbohydrate chains. The human placenta and cancer cells express a common type of carbohydrate chain on their cell surface proteins called chondroitin sulfate (CS). The presence of a CS carbohydrate on cancer cells has allowed us to take advantage of an evolutionarily optimized protein called VAR2CSA from the malaria parasite Plasmodium falciparum. Malarial VAR2CSA binds to distinct CS chains, which are normally only present in the placenta. However, we have recently discovered that VAR2CSA also binds a similar placental-like CS structure broadly present in human cancer. Based on this, we have developed a protein-based technology that can detect and target cancer via their carbohydrate signature. Placenta and cancer has many features in common such as rapid growth, the ability to invade adjacent tissue, and an elaborate formation of blood vessels to feed the tissue. It is therefore tempting to speculate that tumors re-express placental-type CS to accommodate these important cellular processes. In this project we will elucidate the molecular mechanisms behind CS reconfigurations in human prostate and bladder cancer, and establish the role of these CS modifications in tumor cell growth and survival. Our work will provide new insight into the regulation and function of cancer-associated carbohydrates, essential for developing effective therapeutic strategies targeting human cancer.