Mechanism Of Invasion And Metastasis Mediated By LSD1 In Prostate Cancer

Part Ⅰ Relationship between LSD1 expression and E-cadherin expression in prostate cancerObjectives:For the purpose of exploring the relation between the expression of LSD1 and E-cadherin in prostate cancer and their prognostic significance.Methods:The expression of LSD1 and E-cadherin in prostate cancer was detected using immunohistochemistry, and the relation between the expressions of these two molecules was assessed by correlation analysis. In addition, LNCap cell line was treated with Pargyline (an inhibitor of LSD1), and Western blot was used to analyze LSD1 and E-cadherin expression.Results:Expression of LSD1 increased significantly in prostate cancer specimens compared with benign prostatic hyperplasia (P<0.05). Further analysis testified that LSD1 expression was positively correlated with higher Gleason Score, distant metastases, and poor prognosis (P<0.05). Nevertheless, E-cadherin expression decreased significantly in prostate cancer specimens compared with benign prostatic hyperplasia (P<0.05) and was negatively correlated with higher Gleason Score, distant metastases (P<0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression in prostate cancer (rs=-0.486, P= 0.001). Positive LSD1 expression and negative E-cadherin expression were significantly correlated with high 2-year progression (occurrence of castration-resistant prostate cancer) rate and low 5-year survival rate (P<0.05). Moreover, Pargyline inhibited activity of LSD1 and up-regulated E-cadherin expression.Conclusions:High LSD1 expression combined with low E-cadherin expression might be predictors of prostate cancer progression and metastasis. Inhibition of LSDl may be a potential therapeutic target for prevention of prostate cancer.Part Ⅱ Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivoObjectives:This study examined the effect of Pargyline (an inhibitor of LSD1) on the process of EMT and progression of prostate cancer in vitro and in vivo.Methods:SCID mice were injected subcutaneously with LNCap cells. Pargyline was given intraperitoneally or not after castration (implemented with Bilateral orchidectomy), then PSA levels in serum and tumor were determined to assess time to androgen-independent progression.Results:LSD1 expression was up-regulated when PCa progressed to Castration Resistant Prostate Cancer (CRPC). Pargyline reduced LNCap cells migration and invasion ability, and inhibited the process of EMT by up-regulating expression of E-cadherin, and down-regulating expressions of N-cadherin and Vimentin in vitro and in vivo. Although, Pargyline did not change the level of AR, it reduced PSA expression both in vitro and in vivo. Furthermore, Pargyline delayed prostate cancer transition from androgen-dependent to androgen-independent state (CRPC).Conclusions:Inhibition of LSD1 might be a promise adjunctive therapy with androgen deprivation therapy (ADT) for locally advanced or metastatic prostate cancer...