Zitt Matthias, Untergasser Gerold, Amberger Albert, Moser Patrizia, Stadlmann Sylvia, Zitt Marion, Müller Hannes M, Mühlmann Gilbert, Perathoner Alexander, Margreiter Raimund, Gunsilius Eberhard, Ofner Dietmar
Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria.
Dis Markers. 2008;24(2):101-9. doi: 10.1155/2008/160907.
Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3. Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.
Dickkopf-3（Dkk-3）的基因表达已被证明在结直肠癌（CRC）的肿瘤内皮中上调。我们首次分析了Dkk-3蛋白在CRC中的表达及其作为新生血管生成标志物的潜力。我们使用组织微阵列（TMA）研究了403个CRC样本、318个合适的相邻非癌样本和127个正常结直肠样本微血管中的Dkk-3。在具有CD31阳性微血管的癌症样本中，67.7%的样本Dkk-3呈阳性。几乎在所有病例中，所有微血管的内皮细胞均显示Dkk-3染色。Dkk-3阳性样本的平均微血管计数高于Dkk-3阴性样本（P=0.001）。Dkk-3表达随每个样本微血管数量的增加而增加（P<0.0001）。在具有CD31阳性微血管的相邻样本中，所有微血管中有56%的样本Dkk-3呈阳性。与癌症样本相似，Dkk-3阳性的相邻样本的平均微血管计数高于Dkk-3阴性样本（P<0.0001），并且Dkk-3表达也随微血管数量的增加而增加（P<0.0001）。正常黏膜样本中的所有微血管Dkk-3均为阴性。Dkk-3可被认为是新生血管生成中一种假定的促血管生成蛋白，并且可能是CRC中新生血管生成的标志物。进一步的研究将阐明Dkk-3是否是新疗法的靶结构。
