In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma
In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma
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DOI：
10.1038/sj.jid.5700714
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发表时间：
2007-06-01
影响因子：
6.5
通讯作者：
Ostman, Arne
中科院分区：
文献类型：
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作者：
Micke, Patrick;Kappert, Kai;Ostman, Arne
基底细胞癌（BCC）的特点是生长缓慢，几乎没有转移，和强烈的基质依赖性。肿瘤间质中的癌相关成纤维细胞（CAF）影响肿瘤生长、侵袭和转移。为了全面表征BCC在原位癌环境中的CAF，将激光捕获显微切割、线性基因扩增、微阵列分析和定量实时PCR（qRT-PCR）相结合。对显微切割的CAFs和相应的正常毛囊周围成纤维细胞的基因表达进行成对比较，确定了65个基因，这些基因在三个不同患者中的至少两个中显著上调。在注释的基因中，多达13个基因编码分泌蛋白，其中6个先前被认为是各种肿瘤类型中的CAF相关蛋白。选择七种新CAF基因中的四种-基质Gla蛋白、分泌型卷曲相关蛋白2、血管生成素相关蛋白-2和血小板衍生生长因子受体样蛋白-用于通过qRT-PCR进行进一步分析，并且发现在三种独立BCC组织的CAF中频繁上调。对来自鳞状细胞癌、前列腺癌和结肠癌的CAF的分析没有表明这些基因在这些癌症中上调。因此，这项研究验证了一种新的方法，全面表征CAFs在原位环境中的BCC。结果提示，基底细胞癌中CAFs的特异性表达谱可能是疾病特异性病理作用的原因。
Basal cell carcinoma (BCC) is characterized by slow growth, virtual absence of metastases, and strong stroma-dependency. Cancer-associated fibroblasts (CAFs) in the tumor stroma influence tumor growth, invasion, and metastasis. To comprehensively characterize CAFs of BCC in their in situ cancer environment, laser capture microdissection, linear gene amplification, microarray analysis, and quantitative real-time PCR (qRT-PCR) were combined. Pair-wise comparison of gene expression of microdissected CAFs and corresponding normal perifollicular fibroblasts identified 65 genes that were significantly upregulated in at least two of three different patients. Among the annotated genes, as many as 13 genes encoded secreted proteins, of which six were previously implicated as CAF-associated proteins in various tumor types. Four of the seven novel CAF genes matrix Gla-protein, secreted frizzled-related protein 2, angiopoietin-related protein-2, and platelet-derived growth factor receptor-like protein - were selected for further analyses by qRT-PCR and were found to be frequently upregulated in CAFs of three independent BCC tissues. Analyses of CAFs from squamous cell cancer, prostate cancer, and colon cancer did not indicate that these genes were upregulated in these cancers. This study thus validates a novel approach for comprehensive characterization CAFs in their in situ environment of BCC. The results suggest a specific expression profile of CAFs in BCC possibly accounting for disease-specific pathological roles.