Détail du document
Identifiant
oai:www.zora.uzh.ch:236088
Sujet
Institute of Veterinary Pathology Institute of Veterinary Pharmacolo... 570 Life sciences biology Cancer Research, OncologyAuteur
Ettlin, Julia https://orcid.org/0000-0001-6016-4865 Bauer, Alina https://orcid.org/0000-0002-8328-3143 Opitz, Lennart https://orcid.org/0000-0001-7945-6737 Malbon, Alexandra https://orcid.org/0000-0002-5144-3333 Markkanen, Enni https://orcid.org/0000-0001-7780-8233Langue
engEditeur
Springer
Catégorie
Subjects = 05 Vetsuisse Faculty: Institute of Veterinary Pharmacology and Toxicology
Année
2023
Date de référencement
11/10/2023
Mots clés
stroma breast genes identify mammary canine cancer cmts stromalRésumé
Cancer-associated stroma (CAS) is widely recognized to influence development and progression of epithelial tumours including breast cancer.
Canine mammary tumours (CMTs) such as simple canine mammary carcinomas represent valuable models for human breast cancer also with respect to stromal reprogramming.
However, it remains unclear whether and how CAS changes in metastatic tumours compared to non-metastatic ones.
To characterize stromal changes between metastatic and non-metastatic CMTs and identify potential drivers of tumour progression, we analysed CAS and matched normal stroma from 16 non-metastatic and 15 metastatic CMTs by RNA-sequencing of microdissected FFPE tissue.
We identified 1438 differentially regulated genes between CAS and normal stroma, supporting previous results demonstrating stromal reprogramming in CMTs to be comparable with CAS in human breast cancer and validating deregulation of pathways and genes associated with CAS.
Using primary human fibroblasts activated by treatment with TGFβ, we demonstrate some of the strongest expression changes to be conserved in fibroblasts across species.
Furthermore, we identify 132 differentially expressed genes between CAS from metastatic and non-metastatic tumours, with strong changes in pathways including chemotaxis, regulation of apoptosis, immune response and TGFβ signalling and validate deregulation of several targets using RT-qPCR.
Finally, we identify specific upregulation of COL6A5, F5, GALNT3, CIT and MMP11 in metastatic CAS, suggesting high stromal expression of these targets to be linked to malignancy and metastasis of CMTs.
In summary, our data present a resource supporting further research into stromal changes of the mammary gland in relation to metastasis with implications for both canine and human mammary cancer.
Ettlin, Julia, https://orcid.org/0000-0001-6016-4865,Bauer, Alina, https://orcid.org/0000-0002-8328-3143,Opitz, Lennart, https://orcid.org/0000-0001-7945-6737,Malbon, Alexandra, https://orcid.org/0000-0002-5144-3333,Markkanen, Enni, https://orcid.org/0000-0001-7780-8233, 2023, Deciphering Stromal Changes between Metastatic and Non-metastatic Canine Mammary Carcinomas, Springer
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