Singer Christian F, Gschwantler-Kaulich Daphne, Fink-Retter Anneliese, Haas Cornelia, Hudelist Gernot, Czerwenka Klaus, Kubista Ernst
Department of OB/GYN, Division of Special Gynecology, Medical University of Vienna, Vienna, Austria,
Breast Cancer Res Treat. 2008 Jul;110(2):273-81. doi: 10.1007/s10549-007-9725-2. Epub 2007 Sep 26.
Breast cancer is characterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumor-derived fibroblasts display unique phenotypic properties, it is unclear whether they also represent are a specific subpopulation.
Stromal fibroblasts deriving from malignant tissue of 10 women with invasive breast cancer, and from normal breast tissue of 10 women with benign breast disorders, were subjected to differential complementary DNA Microarray Analysis by using a 2,400 gene cDNA array. Individual gene expression pattern were confirmed by RT-PCR.
In a cDNA array that allows to analyze the differential gene expression of more than 2,400 genes, the mRNA expression of 135 genes were increased more than 2 fold in fibroblasts from malignant breast tumors. The majority of these genes encode tumor-promoting cytokines, transcription factors and cell-matrix associated proteins. The mRNA expression of 110 genes decreased to less than 0.5 fold. The remaining 2,155 genes were not significantly altered. RT-PCR performed on individual biopsies from breast cancer and normal breast tissues confirmed the validity of the pooled gene expression signature.
Breast cancer-derived stromal fibroblasts show a distinctive gene expression pattern that differentiates them from normal breast stroma. Our observation of increased expression of tumor promotion-associated genes even in the absence of adjacent malignant epithelium suggests that tumor stroma is comprised of a fibroblastic subpopulation that provides for a microenvironment which supports tumor growth and invasion.
乳腺癌以上皮细胞的恶性转化为特征，但基质细胞在肿瘤发生中也起重要作用。虽然肿瘤来源的成纤维细胞表现出独特的表型特性，但尚不清楚它们是否也代表一个特定的亚群。
从10例浸润性乳腺癌女性的恶性组织以及10例乳腺良性疾病女性的正常乳腺组织中获取基质成纤维细胞，使用2400基因的cDNA阵列进行差异互补DNA微阵列分析。通过逆转录聚合酶链反应（RT-PCR）确认个体基因表达模式。
在一个能够分析2400多个基因差异基因表达的cDNA阵列中，乳腺恶性肿瘤来源的成纤维细胞中135个基因的mRNA表达增加了2倍以上。这些基因中的大多数编码促肿瘤细胞因子、转录因子和细胞基质相关蛋白。110个基因的mRNA表达下降至小于0.5倍。其余2155个基因无明显变化。对乳腺癌和正常乳腺组织的个体活检样本进行的RT-PCR证实了汇总基因表达特征的有效性。
乳腺癌来源的基质成纤维细胞表现出独特的基因表达模式，使其与正常乳腺基质区分开来。我们观察到即使在没有相邻恶性上皮的情况下促肿瘤相关基因的表达也增加，这表明肿瘤基质由一个成纤维细胞亚群组成，该亚群提供了支持肿瘤生长和侵袭的微环境。
