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| Status |
Public on Jul 18, 2018 |
| Title |
Ruxolitinib inhibits Cyclosporine-induced proliferation of cutaneous squamous cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Organ transplant recipients (OTRs) on Cyclosporine A (CSA) are prone to catastrophic cutaneous squamous cell carcinoma (SCC). Allograft-sparing, cancer-targeting systemic treatments are unavailable. We have shown increased risk for catastrophic SCC in OTRs via CSA-mediated induction of Interleukin-22 (IL-22). Herein, we found CSA drives SCC proliferation and tumor growth through IL-22 and JAK/STAT pathway induction. We in turn inhibited SCC growth with an FDA-approved JAK 1/2 inhibitor, Ruxolitinib. In human SCC cells, greatest proliferative response to IL-22 and CSA treatment occurred in non-metastasizing lines. IL-22 treatment upregulated JAK1 and STAT1/3 in A431 SCC cells. JAK/STAT pathway genes were highly expressed in tumors from a cohort of CSA-exposed OTRs, and in SCC with high risk for metastasis. Compared to immunocompetent SCC, genes associated with innate immunity, response to DNA damage and p53 regulation were differentially expressed in SCC from OTRs. In nude mice engrafted with human A431 cells, IL-22 and CSA treatment increased tumor growth and upregulated IL-22 receptor, JAK1 and STAT 1/3 expression. Ruxolitinib treatment significantly reduced tumor volume and reversed the accelerated tumor growth. CSA and IL-22 exacerbate aggressive behavior in SCC. Targeting the IL-22 axis via selective JAK/STAT inhibition may reduce the progression of aggressive SCC in OTRs, without compromising immunosuppression.
In this study, microarray data was used to compare normal skin to immunocompetent SCC, to transplant associated SCC (TSCC)
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| Overall design |
Total RNA was extracted from tissue samples of normal skin (n = 10), immunocompetent SCC (n = 8) and SCC from OTRs (n = 5)
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| Contributor(s) |
Abikhair Burgo M, Carucci JA |
| Citation(s) |
30185657 |
| Submission date |
Jul 17, 2018 |
| Last update date |
Dec 13, 2018 |
| Contact name |
Melody Abikhair |
| Organization name |
NYU School of Medicine
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| Street address |
550 FIRST AVENUE
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| City |
NEW YORK |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA481531 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE117247_RAW.tar |
56.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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