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| Status |
Public on May 05, 2022 |
| Title |
Phenotype screens of genetically engineered mouse models of pancreatic cancer identify a Tgfa-Ccl2-paxillin axis driving human-like perineural invasion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Solid cancers such as pancreatic cancer (PDAC) often exploit nerves for rapid spread. This neural invasion (NI) is an independent prognostic factor in PDAC and the main trigger for local recurrence and severe pain. However, genetically engineered mouse models (GEMM) of PDAC do not adequately represent the morphology of human NI.
Therefore, we performed a systematic morphological screening of mutant mice with combinations of mutant alleles of oncogenes and tumour suppressors from our mouse repository.
In a newly generated TPAC and TPC mouse mutant with pancreas-specific overexpression of transforming growth factor alpha (TGFa) and conditional deletion of p53, we identified human-like NI. To dissect the molecular mechanisms behind, we compared the transcriptome of TPAC and TPC mouse mutants with known KPC and KC mice lacking NI pathology.
Our results revealed strong enrichment of genes encoding the extracellular matrix, including ECM glycoproteins, collagens and proteoglycans involved in biological oxidation, nuclear receptors, and proteins encoding drug metabolism via cytochrome P450 and retinoic acid signaling in TPAC cancer cells.
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| Overall design |
We analysed global RNA expression in pancreatic tumours from mouse PDAC cell lines with high neuroinvasive potential and compared them to non-invasive tumour cells.
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| Contributor(s) |
Demir EI, Istvanffy R |
| Citation(s) |
37607005 |
| |
| Submission date |
May 02, 2022 |
| Last update date |
Sep 18, 2023 |
| Contact name |
Rouzanna Istvánffy |
| E-mail(s) |
rouzanna.istvanffy@tum.de
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| Organization name |
Klinikum rechts der Isar
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| Department |
Department of Surgery
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| Street address |
Ismaningerstr. 22
|
| City |
Munich |
| ZIP/Postal code |
81675 |
| Country |
Germany |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA833954 |
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