|
Academic/Biomedical Research
News & Jobs
|
|
|
|
|
|
|
|
|
|
|
|
|
Free Newsletters
Archive
My Subscriptions
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers
Regional News
US & Canada
Biotech Bay
Biotech Beach
Genetown
Pharm Country
BioCapital
BioMidwest
Bio NC
BioForest
Southern Pharm
BioCanada East
US Device
Europe
Asia
Company Profiles
Research Store
Research Events
Post an Event
Real Estate
Business Opportunities
|
|
|
|
PLoS By Category | Recent
PLoS Articles
|
|
Biochemistry - Immunology - Oncology - Physiology - Urology
|
Interleukin-15 Plays a Central Role in Human Kidney Physiology and Cancer through the ?c Signaling Pathway
Published:
Tuesday, February 21, 2012
Author:
Julien Giron-Michel et al.
by Julien Giron-Michel, Sandy Azzi, Krystel Khawam, Erwan Mortier, Anne Caignard, Aurore Devocelle, Silvano Ferrini, Michela Croce, Hélène François, Lola Lecru, Bernard Charpentier, Salem Chouaib, Bruno Azzarone, Pierre Eid
The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Raß?c complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the ?c-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of ?c-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the ?c/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Raß heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/?c-dependent signaling (STAT5), by co-transfecting ?c and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and ?c-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation).
More...
|
|
|
 |
|
|
|
|
|
|
|
|