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.
Highlights
The majority of all cancers are of epithelial origin and derive from a corrupted epithelial cell population that gives rise to aggressively growing tumour cells
The main aims of our study were, firstly, to characterise the expression of known Cancer-associated stroma (CAS)-associated targets from human cancer in canine mammary tumour associated stroma and, secondly, to understand if large aspects of the underlying biology of CAS could be compared between dog and human breast cancer
Cases with obvious inflammation were excluded to avoid introducing unnecessary variability. With these criteria in mind, we selected a total of 13 canine simple mammary carcinomas, as defined by a board-certified veterinary pathologist (A.M.), from the archives to be included in the analysis
Summary
The majority of all cancers are of epithelial origin and derive from a corrupted epithelial cell population that gives rise to aggressively growing tumour cells. These epithelial tumour cells are not living in an isolated environment, and, far from being self-sufficient, heavily depend on their microenvironment for growth and survival (reviewed in [1]). Stroma serves as an important barrier to prevent epithelial transformation (reviewed in [3]). In response to emerging epithelial cancerous lesions, the stromal compartment undergoes a reprogramming towards a tumour-supportive function, termed cancer-associated stroma (CAS), and plays a key role in cancer initiation and progression [1]. Studies performed in human clinical tumour samples have begun to shed light on mechanisms driving the formation of CAS as well as the molecular dialogue between CAS and tumour cells (e.g., [5,6,7,8])
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