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Int. J. Mol. Sci. 2017, 18(5), 1101; doi:10.3390/ijms18051101

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

1
Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, Winterthurerstr. 260, 8057 Zürich, Switzerland
2
Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Winterthurerstr. 268, 8057 Zürich, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Sanjay K. Srivastava
Received: 14 February 2017 / Revised: 3 May 2017 / Accepted: 17 May 2017 / Published: 20 May 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry. We found that Col1a1 (Collagen1α1), αSMA (alpha Smooth Muscle Actin), FAP (Fibroblast activation protein), PDGFRβ (Platelet-derived growth factor receptor beta), and Caveolin-1 were significantly upregulated in canine CAS, and the expression of CXCL12 (Stromal cell derived factor 1) significantly decreased, whereas MMP2 (Matrix Metalloproteinase 1) and IL6 (Interleukin 6) did not change. Our results suggest strong similarities in CAS biology in canine and human mammary carcinomas but also reveal some differences. To the best of our knowledge, this is the first report to provide a comprehensive expression analysis of the most important CAS markers in canine simple mammary carcinomas and further supports the validity of the dog as model for human cancer. View Full-Text
Keywords: cancer; dog; tumour; mammary carcinoma; tumour stroma; gene expression; cancer-associated stroma; tumour microenvironment cancer; dog; tumour; mammary carcinoma; tumour stroma; gene expression; cancer-associated stroma; tumour microenvironment
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ettlin, J.; Clementi, E.; Amini, P.; Malbon, A.; Markkanen, E. Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas. Int. J. Mol. Sci. 2017, 18, 1101.

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