Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis
Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis
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DOI：
10.1136/jcp.2004.018598
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发表时间：
2005-05-01
影响因子：
3.4
通讯作者：
Holcombe, RF
中科院分区：
文献类型：
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作者：
Byun, T;Karimi, M;Holcombe, RF
背景：Wnt信号失调与癌症有关，包括结肠癌和胃癌。Wnt信号传导的起始受可溶性Wnt拮抗剂（sWAs）调节，包括可溶性卷曲相关蛋白、dickkopf（Dkk）蛋白和Wnt抑制因子-1（Wif 1）。（胃）和下（结肠）胃肠道肿瘤发生。Dkk 1 - 3，Wif 1，和FrzB的表达进行了评估，通过原位RNA杂交的正常和恶性的人胃和结肠组织。结果：正常胃组织中Wif 1、Dkk 1和Dkk 2均不表达。Dkk 3在部分标本中有表达，在胃深腺中表达较强。FrzB在几个正常胃样本中表达，但在匹配的肿瘤标本中不表达。而Dkk 1和FrzB在正常结肠组织中不表达。wif 1在大多数结肠样品中表达，在隐窝基底表达更强。Dkk 3和Dkk 2的表达也集中在隐窝基部。结论：sWA在上、下消化道组织中的表达存在差异。FrzB在胃癌中的缺失表明其作为肿瘤抑制因子。Dkk 3在胃组织中的分级表达，以及Dkk 2、Dkk 3和Wif 1在结肠组织中的分级表达，以及在胃肠道干细胞所在的深胃腺/结肠隐窝基底中的表达增加，表明sWA可能是这些组织中至关重要的Wnt信号传导调节剂，并且可能有助于干细胞池的维持。sWA是胃肠道增殖调节网络的重要组成部分。
Background: Wnt signalling dysregulation has been implicated in cancer, including colon and gastric cancer. Initiation of Wnt signalling is modulated by soluble Wnt antagonists (sWAs), including soluble frizzled related proteins, dickkopf (Dkk) proteins, and Wnt inhibitory factor-1 (Wif1).Aims: To evaluate the role of sWAs in upper ( gastric) and lower ( colon) gastrointestinal tract tumorigenesis.Methods: Dkk1 - 3, Wif1, and FrzB expression was evaluated by in situ RNA hybridisation on normal and malignant human gastric and colon tissues. Expression was graded semiquantitatively.Results: Wif1, Dkk1, and Dkk2 were not expressed in normal gastric tissue. Dkk3 was expressed in some samples, with stronger expression in deep gastric glands. FrzB was expressed in several normal gastric samples, but not in matched tumour specimens. In contrast, Dkk1 and FrzB were not expressed in normal colon. Wif1 was expressed in most colon samples, with stronger expression at crypt bases. Dkk3 and Dkk2 expression was also concentrated at crypt bases. There were no differences between sWA expression in malignant colon and matched normal tissue.Conclusions: sWA expression differed between upper and lower gastrointestinal tract. The loss of FrzB in gastric cancer suggests that it acts as a tumour suppressor. The graded expression of Dkk3 in gastric tissue, and Dkk2, Dkk3, and Wif1 in colon tissue, with increased expression in the deep gastric glands/colonic crypt bases, where gastrointestinal stem cells reside, suggests that sWAs may be crucial Wnt signalling regulators in these tissues, and may contribute to stem cell pool maintenance. sWAs are important components of the gastrointestinal proliferative regulatory network.