title: 22 : 6n-3 DHA inhibits differentiation of prostate fibroblasts into myofibroblasts and tumorigenesis.
abstract: Prostate cancer is one of the most common malignancies in men. Epidemiological and experimental studies have revealed that stromal cells of the tumour microenvironment contribute to the development of prostate cancers, while long-chain n-3 PUFA-enriched diets reduce the risk of this tumour histotype. These findings prompted us to investigate whether DHA, an n-3 PUFA, may abrogate differentiation of prostate fibroblasts into myofibroblasts, the activated form of fibroblasts generally involved in prostate cancer progression. We used the human prostate carcinoma cell line (PC3) as a prostate adenocarcinoma model and found that DHA (1) inhibits α-smooth muscle actin (α-SMA) expression, a typical marker of myofibroblast differentiation, in prostate fibroblasts stimulated in vitro with transforming growth factor-β (TGF-β), (2) blocks the matrix metalloproteinase-2-dependent enhanced invasiveness of PC3 prostate adenocarcinoma cells migrated in a medium conditioned by TGF-β-stimulated prostate fibroblasts, (3) prevents epithelial-mesenchymal transition (EMT) and invasiveness of PC3 cells promoted by a medium conditioned by TGF-β-stimulated prostate fibroblasts, and (4) reduces the growth rate of tumours obtained in immunodeficient animals injected with PC3 cells plus TGF-β-stimulated prostate fibroblasts. Moreover, DHA was found to revert α-SMA expression and the invasiveness-promoting activity exerted in PC3 cells by tumoral-activated fibroblasts. Thus, DHA represents a suitable agent to inhibit prostate myofibroblast differentiation, invasiveness and EMT, two most important tumour-promoting activities involved in the progression of prostate cancer cells.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni 50, 50134              Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchini
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannoni
authors.forename: Sergio
authors.initials: S
authors.lastname: Serni
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
authors.forename: Lido
authors.initials: L
authors.lastname: Calorini
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D058628:Myofibroblasts / Q000473:pathology*; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015525:Fatty Acids, Omega-3; D016212:Transforming Growth Factor beta; D004281:Docosahexaenoic Acids