Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases
Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases
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DOI：
10.1002/ijc.21307
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发表时间：
2006-01-01
影响因子：
6.4
通讯作者：
Brand, K
中科院分区：
文献类型：
--
作者：
Bandapalli, OR;Geheeb, M;Brand, K
宿主细胞反应是肿瘤侵袭的关键决定因素。我们在全基因组范围内分析了裸鼠肝脏中生长的人类结直肠肿瘤（LS174）的未受影响肝脏组织的微解剖组织与侵袭前沿宿主部分的组织之间的基因表达差异。由于Affymetrix微阵列测定的种间杂交程度较低，为15%，我们的异种移植物模型允许区分小鼠和人类来源的基因，即使各自的组织不能单独分离。使用基因本体论（GO）分类，我们能够确定侵袭性前沿肝脏部分上调和下调基因的模式。我们观察到，GO术语“细胞外基质”、“细胞通讯”、“对生物刺激的反应”、“结构分子活性”和“细胞生长”的代表性明显过高，表明宿主细胞对肿瘤侵袭的反应非常明显。在单基因水平上，肝星状细胞（HSC）激活标记在侵袭前沿的肝脏部分被过度代表。免疫组织化学和qPCR证实了HSC的激活，并且与未侵袭的肝组织相比，侵袭前的HSC数量增加。总之，我们的数据证明了在全基因组范围内种间差异基因表达方法的可行性。(c) 2005 Wiley-Liss, Inc。
Host cell reactions are a crucial determinant for tumor invasion. We analyzed on a genomewide scale gene expression differences between microdissected tissues taken from unaffected liver tissue of a human colorectal tumor (LS174) growing in the livers of nude mice and tissue from the host part of the invasive front. Due to the low degree of interspecies cross-hybridization of 15% as determined on Affymetrix microarrays, our xenograft model allowed for the distinction of genes of murine versus human origin even if the respective tissues could not be isolated separately. Using the gene ontology (GO) classification, we were able to determine patterns of up- and downregulated genes in the liver part of the invasive front. We observed a pronounced overrepresentation, e.g., of the GO terms "extracellular matrix," "cell communication," "response to biotic stimulus," "structural molecule activity" and "cell growth," indicating a very pronounced host cell response to tumor invasion. On the single gene level, hepatic stellate cell (HSC) activation markers were overrepresented in the liver part of the invasion front. Immunohistochemistry and qPCR confirmed an activation of HSC as well as an increased number of HSC in the invasive front as compared to the noninvaded liver tissue. In summary, our data demonstrate the feasibility of an interspecies differential gene expression approach on a genomewide scale. (c) 2005 Wiley-Liss, Inc.