1336 PCK3145 SUPPRESSES THE INVASIVE CAPABILITIES OF HUMAN PROSTATE CANCER CELLS INDUCED BY TRANSFORMING GROWTH FACTOR BETA
Bibliographic record
Abstract
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 ...
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.013 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".