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| Status |
Public on Mar 12, 2023 |
| Title |
EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle invasive bladder cancer (MIBC). However, impact on bladder cancer with substantial squamous differentiated (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n=125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative ‘‘Achilles heel’’ of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response by upregulating EGFR and ERBB3 expression. Hence, our findings give novel insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of combined anti-EGFR and chemotherapeutic regimens in squamous bladder cancers with wild-type EGFR-overexpression.
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| Overall design |
Tumor tissue of an individual diagnosed with a pure SCC was obtained from the RWTH centralized biomaterial bank (RWTH cBMB) for SCC-tumor cell (p-SCC) isolation. Primary cells derived from pure SCC (p-SCC) tissue were established as a cell culture ex vivo model. p-SCC cells (n=1) were characterized and compared with the original tumor tissue (n=1) by whole transcriptomic analysis. SCaBER (n=1) and J82 cell lines (n=1) served as squamous and urothelial-like controls.
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| Contributor(s) |
Rose M, Denecke B, Gaisa NT |
| Citation missing |
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| |
| Submission date |
Mar 13, 2020 |
| Last update date |
Mar 14, 2023 |
| Contact name |
Bernd Denecke |
| E-mail(s) |
[email protected]
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| Phone |
+49 241 8089918
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| Organization name |
RWTH Aachen University
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| Department |
IZKF Aachen
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| Street address |
Pauwelsstrasse 30
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| City |
Aachen |
| State/province |
NRW |
| ZIP/Postal code |
52074 |
| Country |
Germany |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA612537 |
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