Unravelling the immunomodulatory role of hyaluronan in prostate cancer development

Prostate cancer (PCa) is implicated as the most frequently diagnosed non-skin cancer and the second-leading cause of cancer-related death in males. Despite the efficacy of androgen-deprivation therapy (ADT), a sizable portion of patients undergo castration-resistant prostate cancer (CRPC), and the reason can stem from not taking into account the critical and interactive relation of cancer cells with the tumor microenvironment (TME). Preliminary RNA-seq and immunohistochemistry data illustrated an alteration of hyaluronan metabolism that was highly significant in Pten-null compared to the wild-type mice. The aim of my thesis project was to study the interaction between the hyaluronan metabolism and immune system and the contribute of hyaluronic acid in PCa development. Our results suggested a pivotal immunomodulatory role of hyaluronan in PCa progression. In parallel, we treated human and murine PCa cell lines with 4-MU, a of hyaluronan synthesis. Results demonstrated a significant reduction of cell proliferation, associated with the downregulation of Has1 and Has2 expression and cell cycle arrest. Furthermore, ELISA results showed that there was also a significant reduction in hyaluronan production. Taken together, these data confirmed the relation between hyaluronan metabolism and the TME and suggest a potential immunomodulatory role of this component in the PCa progression.