Grant: Doctoral: Vanier Canada Graduate Scholarships

Supervisor: Dr. Mads Daugaard, UBC. Cancer cells are coated with chains of sugar molecules which are collectively called the glycocalyx. The glycocalyx plays an important role in cell-to-cell signaling and communication, and harbors growth factors to encourage cell survival and division. Cancer cells have the ability to reconfigure the glycocalyx to support various aspects of disease progression. In prostate cancer, a portion of the glycocalyx is made up of a sugar called chondroitin sulfate (CS) which is regulated by androgens, the male sex hormone. Androgens are required for and stimulate prostate cancer growth in early stages. However, tumors often adapt alternative mechanisms to survive and grow, even without androgens present. Increased amounts of chondroitin sulfate has been correlated with increased prostate cancer growth in various studies, but the exact role and mechanism of CS remains unclear. In a recent publication by our team in Nature Communication, we showed that chondroitin sulfate becomes particularly important in the context of androgen-deprivation therapy. When prostate cancer cells are deprived of androgens, they rely on CS to survive, proliferate, and invade. We surprisingly found that in the absence of androgens, prostate cancer cells change the shape of the glycocalyx. It becomes thicker, and forms dot structure at its cell's basement. We also observed in various prostate cancer patient datasets that enzymes responsible for elongating and putting sulfur of CS chains have higher level of expression in patients with risk to develop metastasis. We believe this finding could unleash new understanding on prostate cancer biology, and provides a strong rationale for studying chondroitin sulfate in prostate cancer. In this project, we aim to investigate and identify changes in shape and content of CS-containing glycocalyx on prostate cancer cells and the role of CS in metastases to inform new therapeutic strategies.