Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma
Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma
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DOI：
10.1136/mp.55.4.220
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发表时间：
2002-08-01
期刊：
影响因子：
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通讯作者：
Truong, T
中科院分区：
文献类型：
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作者：
Holcombe, RF;Marsh, JL;Truong, T
目的：Wnt信号通路与结肠癌的发生密切相关。虽然激活基因突变的腺瘤性息肉病大肠杆菌（APC）和β-连环蛋白是明确相关的结肠癌，很少被理解的上游分泌的配体（Wnt）和它们的受体（卷曲，Fz）在这一过程中的作用。在其他系统中，增加的Wnt信号传导已被证明改变该途径的组分的表达。本研究的目的是测试的假设，结肠癌的特点是异常表达的特定Wnt基因和Fz receptors.Methods：Wnt基因的表达进行了评估原位，反义RNA杂交在石蜡包埋的正常和恶性的人类结肠组织的样品与探针特异性的个别Wnt基因。结果：Fz 1和Fz 2在结肠癌组织中的表达有明显变化，Fz 1和Fz 2在结肠癌组织中的表达无明显变化，而Fz 2在结肠癌组织中的表达无明显变化。例如，在结肠癌中检测到Wnt 2 mRNA，但在正常结肠粘膜中检测不到。Wnt 5a在正常粘膜中的差异表达也被注意到，与腔绒毛相比，在隐窝基部的表达增加，并且在结肠癌中的表达略微增加。Wnt 7a在正常和恶性结肠组织中均表现出最低表达，而其他Wnt配体包括Wnt 1、4、5 b、6、7 b和10 b在正常和恶性结肠组织中均同等且强烈表达。在定义细胞反应和表型时，Fz受体的类型和分布可能与Wnt配体表达的模式一样重要。Fz受体1和2在正常结肠粘膜和分化良好的肿瘤中没有表达。然而，分化差的肿瘤表现出高度的Fz受体表达，特别是在边缘的细胞invasion.Conclusions：这些数据表明，表达的Wnt信号转导通路的成员，不同的APC和β-连环蛋白，是不可分割的与结肠癌发生的过程。Wnt 2和可能的Wnt 5a可能参与从正常粘膜到癌症的进展，并且Fz 1/2受体的表达可能参与与肿瘤侵袭相关的过程。这些Wnts和Fz受体的表达改变可能被证明是有用的结肠癌患者的预后或诊断标志物。
Aims: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors.Methods: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues.Results: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion.Conclusions: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.