1336 PCK3145 SUPPRESSES THE INVASIVE CAPABILITIES OF HUMAN PROSTATE CANCER CELLS INDUCED BY TRANSFORMING GROWTH FACTOR BETA
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Résumé
You have accessJournal of UrologyProstate Cancer: Basic Research (VI)1 Apr 20131336 PCK3145 SUPPRESSES THE INVASIVE CAPABILITIES OF HUMAN PROSTATE CANCER CELLS INDUCED BY TRANSFORMING GROWTH FACTOR BETA Qiang Zhang, Bob Lee, Xiao Lin, Brian Helfand, Zhihua Wang, Helene Dulude, Chandra Panchal, Susan Slovin, James Kozlowski, Gregory Sivolapenko, Thimothy Michael Kuzel, Charles B Brendler, William J Catalona, Yinglu Guo, Lin Chen, Ximing J. Yang, Borko Jovanovic, and Chung Lee Qiang ZhangQiang Zhang Chicago, IL More articles by this author , Bob LeeBob Lee Chicago, IL More articles by this author , Xiao LinXiao Lin Fuzhou, Fujian, China, People's Republic of More articles by this author , Brian HelfandBrian Helfand Evanston, IL More articles by this author , Zhihua WangZhihua Wang Wuhan, Hubei, China, People's Republic of More articles by this author , Helene DuludeHelene Dulude Montreal, Canada More articles by this author , Chandra PanchalChandra Panchal Montreal, Canada More articles by this author , Susan SlovinSusan Slovin New York, New York More articles by this author , James KozlowskiJames Kozlowski Chicago, IL More articles by this author , Gregory SivolapenkoGregory Sivolapenko Patras, Greece More articles by this author , Thimothy Michael KuzelThimothy Michael Kuzel Chicago, IL More articles by this author , Charles B BrendlerCharles B Brendler Evanston, IL More articles by this author , William J CatalonaWilliam J Catalona Chicago, IL More articles by this author , Yinglu GuoYinglu Guo Beijing, China, People's Republic of More articles by this author , Lin ChenLin Chen Chicago, IL More articles by this author , Ximing J. YangXiming J. Yang Chicago, IL More articles by this author , Borko JovanovicBorko Jovanovic Chicago, IL More articles by this author , and Chung LeeChung Lee Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2690AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastases are responsible for mortality in prostate cancer (PCa). Previously, we reported that Transforming growth factor beta (TGF-β) induces epithelial-to-mesenchymal transition (EMT) and is associated with PCa metastases and biochemical recurrence. The human prostate secretory protein (PSP-94) is secreted by benign prostate cells and non-aggressive PCa. In this study, we explored the potential of migration inhibition for CaP by PCK3145 (a synthetic mimetic peptide of PSP-94) which may suppress TGF-β induced EMT. METHODS Human PCa cell lines PC-3, DU145 and PC-3M-LN4 and benign prostate cell RWPE1 were used for western blot and migration assays. All cells were treated with PCK3145 and/or TGF-β. For some experiments, cells expressing TGF-â domain negative type II receptor (Tβ RIIDN) were used. Four different treatment groups were assigned to each cell line: Group 1-no treatment (control); Group 2-treatment with TGF-β (10ng/mL) for 48 hours; Group 3-treatment with PCK3145 (100ug/mL) for 48 hours; and Group 4 – treatment with both TGF-β and PCK3145 for 48 hours. Immunohistochemical analyses were performed using primary antibodies against markers of the EMT including vimentin, laminin receptor (LR) and MMP-9. Cell invasion assays were performed in a 24-well matrigel transwell chamber (8-mm pore size). The invaded cells were counted with a light microscope under high magnification objective (100x) and were measured at OD560nm in a plate reader after treatment with the extraction solution. RESULTS Treatment of PCK3145 significantly decreases PCa migration (20 fold lower in PC-3 cells and 2 folds lower in DU145 cells; p<0.001). In addition, PCK3145 inhibits migration induced by TGF-β (30% inhibition for PC-3 cells, and 60% inhibition for DU145 cells; p<0.001). In consistent with the migration assay, analysis of cells exposed to both TGF-β and PCK3145, suppresses TGF-β induced vimentin expression, but not MMP-9 expression in DU145 and PC-3 cells. Treatment of TGF-β alone resulted in significant down-regulation of LR in both DU-145 and PC-3. However, LR was significantly up-regulated in in these cells by treatment of PCK3145 and by blockade of the TGF-β signaling through TβRIIDN. CONCLUSIONS We previously reported TGF-β induced EMT is associated with aggressive phenotypes of PCa. The present findings suggest that PCK3145 may inhibit TGF-β induced vimentin expression and invasion. Investigation of this peptide as an effective anti-tumor metastasis agent is warranted. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e545-e546 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiang Zhang Chicago, IL More articles by this author Bob Lee Chicago, IL More articles by this author Xiao Lin Fuzhou, Fujian, China, People's Republic of More articles by this author Brian Helfand Evanston, IL More articles by this author Zhihua Wang Wuhan, Hubei, China, People's Republic of More articles by this author Helene Dulude Montreal, Canada More articles by this author Chandra Panchal Montreal, Canada More articles by this author Susan Slovin New York, New York More articles by this author James Kozlowski Chicago, IL More articles by this author Gregory Sivolapenko Patras, Greece More articles by this author Thimothy Michael Kuzel Chicago, IL More articles by this author Charles B Brendler Evanston, IL More articles by this author William J Catalona Chicago, IL More articles by this author Yinglu Guo Beijing, China, People's Republic of More articles by this author Lin Chen Chicago, IL More articles by this author Ximing J. Yang Chicago, IL More articles by this author Borko Jovanovic Chicago, IL More articles by this author Chung Lee Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,013 | 0,003 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».