title: Characterization and sub-cellular localization of SS1R, SS2R, and SS5R in human late-stage prostate cancer cells: effect of mono- and bi-specific somatostatin analogs on cell growth.
abstract: Somatostatin (SST) and SST receptors (SS1R, SS2R, SS3R, SS4R and SS5R) appear to play a significant role in the progression of human prostate cancer (PCa), which is associated with heterogeneity of SSRs expression and specific cell localization as we already demonstrated in the LNCaP cell line, an in vitro model of human androgen-dependent PCa. In this study, PC-3 and DU-145 human castration-resistant PCa cells were found to express all SSRs, while LNCaP expressed all but SS4R. A 48-h treatment with BIM-23244 (SS2R/SS5R) or BIM-23926 (SS1R) SST analogs was more effective in inhibiting cell proliferation, compared to BIM-23120 (SS2R), BIM-23206 (SS5R) and BIM-23704 (SS1R/SS2R). BIM-23926 (SS1R) treatment increased the amount of p21 and decreased phosphorylated (p) ERK1/2. BIM-23244 (SS2R/SS5R) led to p21 increment only in PC-3 cells, and to pERK1/2 reduction in both cell lines. SS1R/SS2R and SS2R/SS5R receptor dimers were natively present on cell membrane and their amount was increased by BIM-23704 (SS1R/SS2R) or BIM-23244 (SS2R/SS5R) treatment, respectively. SS1R, SS2R and SS5R were differently distributed among nuclear, lysosomal and microsomal compartment, according to their different recycling dynamics. These results show that, in PC-3, DU-145 and LNCaP cells, activation of SS1R and SS2R/SS5R leads to relevant antiproliferative effects.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ruscica
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Magni
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Steffani
authors.affiliation: Department of Internal Medicine and Medical Specialities & Center of Excellence for Biomedical Research, IRCCS AOU San Martino-IST, Università di Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gatto
authors.affiliation: Department of Internal Medicine and Medical Specialities & Center of Excellence for Biomedical Research, IRCCS AOU San Martino-IST, Università di Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Albertelli
authors.affiliation: Pathophysiology and Transplantation, Università degli Studi di Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rametta
authors.affiliation: Pathophysiology and Transplantation, Università degli Studi di Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Valenti
authors.affiliation: Department of Internal Medicine and Medical Specialities & Center of Excellence for Biomedical Research, IRCCS AOU San Martino-IST, Università di Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ameri
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Magnaghi
authors.affiliation: Biomeasure Incorporated/IPSEN, Milford, MA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Culler
authors.affiliation: Department of Internal Medicine and Medical Specialities & Center of Excellence for Biomedical Research, IRCCS AOU San Martino-IST, Università di Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Minuto
authors.affiliation: Department of Internal Medicine and Medical Specialities & Center of Excellence for Biomedical Research, IRCCS AOU San Martino-IST, Università di Genova, Italy. Electronic address: ferone@unige.it.
authors.forename: D
authors.initials: D
authors.lastname: Ferone
authors.affiliation: Department of Internal Medicine and Medical Specialities & Center of Excellence for Biomedical Research, IRCCS AOU San Martino-IST, Università di Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Arvigo
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D009928:Organ Specificity; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017481:Receptors, Somatostatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C519495:BIM 23120; C519496:BIM 23206; C519494:BIM 23926; C423390:BIM-23244; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D054462:p21-Activated Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: 5′-bromo-2′deoxyuridine; ATP; BrdU; CDS; CTR; Cell proliferation; FAM; IGF; MAPK; P; PCa; PDI; Prostate cancer; SSAs; SSR; SST; SSTR; Somatostatin; Somatostatin analogs; Somatostatin receptor dimerization; Somatostatin receptors; adenosine triphosphate; coding sequences; control; fluorescent dye 6-carboxy-fluorescein; human somatostatin receptor (mRNA); human somatostatin receptor (protein); insulin-like growth factor; mitogen-activated protein kinase; phosphorylated; prostate cancer; protein disulfide isomerase; somatostatin; somatostatin analogs