Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas.
Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas.
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DOI：
10.3390/ijms18051101
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发表时间：
2017-05-20
影响因子：
5.6
通讯作者：
Markkanen E
中科院分区：
文献类型：
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作者：
Ettlin J;Clementi E;Amini P;Malbon A;Markkanen E
癌症相关间质（CAS）在癌症的发生和发展中起着关键作用。自发发生的犬乳腺癌被认为是人类乳腺癌的良好模型。考虑到CAS对人类癌症的重要性，它可能在犬肿瘤中也起着核心作用。然而，到目前为止，犬CAS缺乏表征，并且尚不清楚犬和人类肿瘤CAS之间的生物学是否具有可比性。在这项原理验证研究中，使用激光捕获显微切割，我们从13只福尔马林固定石蜡包埋的犬单纯性乳腺癌中分离出CAS和正常间质，并通过RT-qPCR（逆转录定量PCR）分析了7种已知人类CAS标志物的表达，并通过免疫组化验证了一些靶标。我们发现，在犬CAS中，Col 1a 1（胶原1 α1）、αSMA（α平滑肌肌动蛋白）、FAP（成纤维细胞活化蛋白）、PDGFRβ（血小板衍生生长因子受体β）和小窝蛋白-1显著上调，CXCL 12（基质细胞衍生因子1）的表达显著降低，而MMP 2（基质金属蛋白酶1）和IL 6（白细胞介素6）没有变化。我们的研究结果表明，在CAS生物学在犬和人乳腺癌的强烈相似性，但也揭示了一些差异。据我们所知，这是第一份报告，提供了一个全面的表达分析，最重要的CAS标志物在犬单纯性乳腺癌，并进一步支持狗作为人类癌症模型的有效性。
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.