233 ACTIVATION OF ADIPONECTIN RECEPTOR 1 (ADIPOR1) WHICH IS UNDER-EXPRESSED IN KIDNEY CANCER INDUCES TUMOR SUPRESSION
Bibliographic record
Abstract
You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011233 ACTIVATION OF ADIPONECTIN RECEPTOR 1 (ADIPOR1) WHICH IS UNDER-EXPRESSED IN KIDNEY CANCER INDUCES TUMOR SUPRESSION Nir Kleinmann, Jian Ping Lu, Laura Beatty, Daniel Gallino, Helga Duivenvoorden, Feng Hou, Richard Austin, Anil Kapoor, and Jehonathan Pinthus Nir KleinmannNir Kleinmann Hamilton, Canada More articles by this author , Jian Ping LuJian Ping Lu Hamilton, Canada More articles by this author , Laura BeattyLaura Beatty Hamilton, Canada More articles by this author , Daniel GallinoDaniel Gallino Hamilton, Canada More articles by this author , Helga DuivenvoordenHelga Duivenvoorden Hamilton, Canada More articles by this author , Feng HouFeng Hou Hamilton, Canada More articles by this author , Richard AustinRichard Austin Hamilton, Canada More articles by this author , Anil KapoorAnil Kapoor Hamilton, Canada More articles by this author , and Jehonathan PinthusJehonathan Pinthus Hamilton, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.302AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Circulating levels of adiponectin, a hormone secreted solely by adipose tissue, have been shown clinically to inversely correlate with metastatic progression of renal cell carcinoma (RCC) but the tumor expression of the adiponectin receptors and their role in adiponectin mediated RCC suppression are currently unknown. METHODS The human CRL-1932 and murine CCL-142 RCC cell lines were used as models. The protein expression levels of the adiponectin receptor AdipoR1 were measured in the tumor and compared to that in the normal parenchyma in 14 patients with clear cell RCC. Secretion of VEGF, MMP2&9 and their inhibitors (TIMP1&2) were measured. MMP2&9 activities and the cell's invasion and migration capacities were measured using enzymatic and basement membrane invasion assays, respectively. These studies were repeated following stable transfection of CRL-1932 cells with 5'-AMP-activated protein kinase alpha specific or control short hairpin RNA (shRNA). The effect of adiponectin on the activation of Akt, AMPK, the mammalian target of rapamycin- mTOR1 and S6K was also examined. CCL-142 cells, stably expressing AdipoR1 specific ShRNA or scrambled ShRNA (control) were injected s.c to C57BL mice and followed for their in-vivo growth. RESULTS Adiponectin inhibited the secretion of VEGF and MMP2&9 while it mediated the increased secretion of TIMP1&2 in a dose-dependent manner. Consequently, the reduced enzymatic activity of MMP2&9 inhibited the cell's invasion and migration potential. These effects were induced by AMPK activation and mTOR inhibition in an Akt independent manner. These tumour suppressive effects were attenuated by AMPKα or AdipoR1 but not AdipoR2 knock down. Likewise, In 11/14 (79%) of the patients examined AdipoR1 expression was reduced compared to the their normal renal tissue. Knock down of AdipoR1 expression accelerated the in-vivo growth of RCC implants. CONCLUSIONS Adiponectin induces its tumor suppression via activation of AMPK through AdipoR1. The entire adiponectin hormonal axis (the hormone-adiponectin and its receptor-AdipoR1) is under activated in RCC. Molecules that can activate AMPK (like metformin) or inhibit mTOR (like Everolimus) may have a role in patients with hypo-adiponectinemia or low tumor expression of AdipoR1 who are at risk for metastatic disease. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e95 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nir Kleinmann Hamilton, Canada More articles by this author Jian Ping Lu Hamilton, Canada More articles by this author Laura Beatty Hamilton, Canada More articles by this author Daniel Gallino Hamilton, Canada More articles by this author Helga Duivenvoorden Hamilton, Canada More articles by this author Feng Hou Hamilton, Canada More articles by this author Richard Austin Hamilton, Canada More articles by this author Anil Kapoor Hamilton, Canada More articles by this author Jehonathan Pinthus Hamilton, Canada 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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.027 | 0.005 |
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".