A glucosamine derivative affects metastatic activity in two prostate cancer cell lines by stimulating Maspin expression

Prostate Cancer (CaP) is the most common male tumor and is the third leading cause of cancer death, with an incidence of 1.28 million cases worldwide, according to the data collected by the Global Cancer Observatory in 2018. PC3 and LNCaP cell lines represent suitable models to study CaP development, due to their different metastatic origin and their distinct sensitiveness to androgen signaling. PC3 is a hormone-insensitive cell line isolated from a vertebral metastatic prostatic tumor. It lacks of androgen receptor (AR) and its abnormal growth could be attributed to enhanced expression levels of TGF-α, EGF, and EGF-R. LNCaP cell line was isolated from a human metastatic prostate adenocarcinoma found in a lymphnode. It expresses a T877A mutated AR form, which results in an enhanced binding affinity for several steroid compounds. Both cell lines present very low basal levels of Maspin expression. Maspin, an unusual member of the Serine Proteases superfamily, has been characterized as a class II tumor suppressor gene in many cancer types, among them CaP, due to its ability to inhibit cell invasiveness and proliferation and to increase apoptosis, thus inhibiting metastasis. In normal prostate epithelial cells, Maspin is highly expressed, whereas in prostate cancer cells its expression is almost completely suppressed. Previously in our laboratory, a glucosamine derivative, NCPA, has been proved to be effective in stimulating Maspin expression and to induce its nuclear localization in an osteosarcoma cell line, 143B. The aim of my PhD project was to evaluate the ability of NCPA to affect metastatic activity in two prostate cancer cell lines, the hormone-insensitive PC3 and the hormone-sensitive LNCaP cells, respectively representative of late-stage and early-stage CaP.