Academic paper by Mr. Ota, a third-year doctoral course student at Graduate School of Science and Engineering, was published in U.S. scientific journal Scientific Reports

Mr. Hayato Ota, a third-year doctoral course student at Soka University Graduate School of Science and Engineering (Prof. Shoko Nishihara's research group), has found that prostate cancer acquires castration resistance via 3-O-sulfated heparan sulfate. The results of this research were published on July 18, 2023, in the open-access journal Scientific Reports by Nature Research.

Prostate cancer is a common cancer among men and grows via the male hormone androgen. Common treatments include androgen deprivation therapy such as castration, which cuts off the hormones that cause prostate cancer growth and suppresses its proliferation. However, some prostate cancers survive as castration-resistant prostate cancers that can grow in the absence of hormones, increasing the risk of death. As of now, there is no effective treatment for castration-resistant prostate cancer. Instead of androgen signaling, castration-resistant prostate cancer is known to grow through other signaling pathways such as epidermal growth factor receptor (EGFR), IL-6, and Wnt signaling. However, the detailed mechanism has not been clarified. In this study, we focused on heparan sulfate, a type of glycosaminoglycan that functions as a co-receptor for signal transduction, to analyze the function of heparan sulfate in the growth of castration-resistant prostate cancer.

Recently, it has been known that heparan sulfate functions differently depending on the sulfate modification pattern. In this study, we revealed that the expression levels of 3-O-sulfated heparan sulfate and HS 3-O-sulfotransferase 1 (HS3ST1) were increased in castration-resistant prostate cancer cells. We carried out a knockdown experiment on HS3ST1 and found that EGF and heparin-binding EGF (HB-EGF) bind to EGFR via 3-O-sulfated heparan sulfate and activate signaling in castration-resistant prostate cancer cells. It is well known that HB-EGF binds to heparan sulfate, but the fact that EGF, which was previously thought not to bind to heparan sulfate, activates EGFR signaling via 3-O-sulfated heparan sulfate is noteworthy. Furthermore, we have shown that Gefitinib, an inhibitor of EGFR signaling, is more effective against prostate cancer tumors in castrated mice.

This study elucidates the mechanism by which prostate cancer acquires castration resistance, and the results of this study are expected to lead to more effective treatment of castration-resistant prostate cancer. This work was partially supported by AMED under grant number JP20ae0101037 and by a joint research grant from Soka University Glycan and Life System Integration Center (GaLSIC).