title: Leuprorelin acetate affects adhesion molecule expression in human prostate cancer cells.
abstract: Reduced cell-cell adhesion allows malignant epithelial cells to invade the basal membrane and penetrate the stroma. This implies the potential of the cells to escape from the primary tumor as well as spreading ability. Herein, we investigated the effects of leuprorelin acetate (LA), a GnRH agonistic analogue, alone or in combination with dihydrotestosterone (DHT), on the expression of molecules involved in cell adhesion (E-cadherin, N-cadherin, α-, β- and γ-catenin) or in migration/invasion (c-met, CD44v6 and caveolin-1) in androgen-sensitive (LNCaP) and -insensitive (PC-3) prostate cancer (CaP) cells. We demonstrated by immunoblotting that, in LNCaP cells, molecules present in the adherens junctions (E-cadherin, α-, β- and γ-catenin) were expressed, while α-catenin was absent in PC-3 cells which expressed N-cadherin and c-met. In LNCaP cells, no changes in E-cadherin levels were produced by 10(-9) M DHT while LA (10(-11) or 10(-6) M) up-regulated the protein level (up to 26-30% after 48 h). In the same cells, β- and γ-catenin expression was enhanced either by DHT (24 and 20%, respectively) or LA (up to 18 and 40%, respectively), while α-catenin was not affected. Antagonistic effects were consistently observed between DHT and LA when the two hormones were jointly administered to the cells. Consistent results were obtained by immunocytochemistry. Co-immunoprecipitation analysis, used to verify the integrity of the LNCaP cell adhesion complex, demonstrated the association of E-cadherin with catenins. In PC-3 cells, adhesion molecule expression, analyzed by immunoblotting, was unaffected by LA, while a down-regulation of c-met (up to 28%) was observed after 24 h of treatment but which did not hold up over time (48-144 h). Our findings demonstrate the efficacy of LA in upregulating E-cadherin, β- and γ-catenin in LNCaP cells. This effect, that may be considered as another aspect of the direct antitumor activity of the GnRH analogue in hormone-dependent CaP cells, may contribute to maintenance/restoration of the normal tissue architecture counteracting the tumor cell spreading tendency.
authors.affiliation: Institute of Histology and Embryology, School of Medicine, Catholic University of the Sacred Heart, I-00168 Rome, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Angelucci
authors.forename: Gina
authors.initials: G
authors.lastname: Lama
authors.forename: Fortunata
authors.initials: F
authors.lastname: Iacopino
authors.forename: Gigliola
authors.initials: G
authors.lastname: Sica
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015815:Cell Adhesion Molecules; D013196:Dihydrotestosterone; D016729:Leuprolide