title: Gene signatures distinguish stage-specific prostate cancer stem cells isolated from transgenic adenocarcinoma of the mouse prostate lesions and predict the malignancy of human tumors.
abstract: The relevant social and economic impact of prostate adenocarcinoma, one of the leading causes of death in men, urges critical improvements in knowledge of the pathogenesis and cure of this disease. These can also be achieved by implementing in vitro and in vivo preclinical models by taking advantage of prostate cancer stem cells (PCSCs). The best-characterized mouse model of prostate cancer is the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice develop a progressive lesion called prostatic intraepithelial neoplasia that evolves into adenocarcinoma (AD) between 24 and 30 weeks of age. ADs often metastasize to lymph nodes, lung, bones, and kidneys. Eventually, approximately 5% of the mice develop an androgen-independent neuroendocrine adenocarcinoma. Here we report the establishment of long-term self-renewing PCSC lines from the different stages of TRAMP progression by application of the neurosphere assay. Stage-specific prostate cell lines were endowed with the critical features expected from malignant bona fide cancer stem cells, namely, self-renewal, multipotency, and tumorigenicity. Notably, transcriptome analysis of stage-specific PCSCs resulted in the generation of well-defined, meaningful gene signatures, which identify distinct stages of human tumor progression. As such, TRAMP-derived PCSCs represent a novel and valuable preclinical model for elucidating the pathogenetic mechanisms leading to prostate adenocarcinoma and for the identification of molecular mediators to be pursued as therapeutic targets.
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzoleni
authors.forename: Elena
authors.initials: E
authors.lastname: Jachetti
authors.forename: Sara
authors.initials: S
authors.lastname: Morosini
authors.forename: Matteo
authors.initials: M
authors.lastname: Grioni
authors.forename: Ignazio Stefano
authors.initials: IS
authors.lastname: Piras
authors.forename: Mauro
authors.initials: M
authors.lastname: Pala
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bulfone
authors.forename: Massimo
authors.initials: M
authors.lastname: Freschi
authors.forename: Matteo
authors.initials: M
authors.lastname: Bellone
authors.forename: Rossella
authors.initials: R
authors.lastname: Galli
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D018703:Founder Effect; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: Cancer; Cancer stem cells; Gene expression; Neoplastic stem cell biology