Deciphering Stromal Changes between Metastatic and Non-metastatic Canine Mammary Carcinomas

Julia Ettlin, Alina Bauer, Lennart Opitz, Alexandra Malbon, Enni Markkanen

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Article number14
Pages (from-to)1-16
Number of pages16
JournalJournal of Mammary Gland Biology and Neoplasia
Volume28
Issue number1
Early online date1 Jul 2023
DOIs
Publication statusE-pub ahead of print - 1 Jul 2023

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Animals
  • Dogs
  • Mammary Neoplasms, Animal/genetics
  • Carcinoma
  • Apoptosis
  • Fibroblasts
  • Transforming Growth Factor beta

Fingerprint

Dive into the research topics of 'Deciphering Stromal Changes between Metastatic and Non-metastatic Canine Mammary Carcinomas'. Together they form a unique fingerprint.

Cite this