title: Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis.
abstract: Relaxin (RLN) is a small peptide hormone expressed in several cancers of reproductive and endocrine organs. Increased expression of RLN in prostate cancer correlates with aggressive cancer. RLN G-protein-coupled receptor (RLN family peptide receptor 1, RXFP1) is expressed in both androgen receptor (AR)-positive and -negative prostate cancers as well as in prostate cancer cell lines. RLN behaves as a cell growth factor and increases invasiveness and proliferation of cancer cells in vitro and in vivo. The objective of this study is to determine whether downregulation of RXFP1 expression using small interfering RNA (siRNA) reduces cancer growth and metastasis in a xenograft model of prostate cancer. We used two well-characterized prostate adenocarcinoma cell lines, AR-positive LNCaP cells and AR-negative PC3 cells. The tumors were established in nude male mice by s.c. injections. Intratumoral injections of siRNAs loaded on biodegradable chitosan nanoparticles led to a downregulation of RXFP1 receptor expression and a dramatic reduction in tumor growth. In LNCaP tumors, the siRNA treatment led to an extensive necrosis. In PC3 xenografts treated with siRNA against RXFP1, the smaller tumor size was associated with the decreased cell proliferation and increased apoptosis. The downregulation of RXFP1 resulted in significant decrease in metastasis rate in PC3 tumors. Global transcriptional profiling of PC3 cells treated with RXFP1 siRNA revealed genes with significantly altered expression profiles previously shown to promote tumorigenesis, including the downregulation of MCAM, MUC1, ANGPTL4, GPI, and TSPAN8. Thus, the suppression of RLN/RXFP1 may have potential therapeutic benefits in prostate cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
authors.forename: Irina U
authors.initials: IU
authors.lastname: Agoulnik
authors.forename: Anne
authors.initials: A
authors.lastname: Truong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Elena M
authors.initials: EM
authors.lastname: Kaftanovskaya
authors.forename: Rhea
authors.initials: R
authors.lastname: Pereira
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Agoulnik
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000628:therapy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D034741:RNA, Small Interfering; D011897:Random Allocation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014162:Transfection; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D034741:RNA, Small Interfering; C478103:RXFP1 protein, mouse; D043562:Receptors, G-Protein-Coupled