Characteristics of CD44 alternative splice pattern in the course of human colorectal adenocarcinoma progression.
Characteristics of CD44 alternative splice pattern in the course of human colorectal adenocarcinoma progression.
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DOI：
10.1186/1476-4598-11-83
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发表时间：
2012-11-14
期刊：
影响因子：
37.3
通讯作者：
Rásó E
中科院分区：
文献类型：
--
作者：
Bánky B;Rásó-Barnett L;Barbai T;Tímár J;Becságh P;Rásó E
CD44被认为是“一种”转移相关基因，尽管事实上它是通过选择性剪接从单个基因产生的一组分子的总称。然而，在结直肠癌以及其他肿瘤类型的文献中，很少考虑到上述情况，导致关于其在肿瘤进展中可能的作用的混乱和矛盾的结果。我们采用一系列PCR反应和新一代测序方法比较了三种不同基因型的人结直肠癌细胞系（HT 25、HT 29、HCT 116）的CD 44选择性剪接模式（ASP），并鉴定了一种结直肠腺癌特异性CD 44 ASP。在我们的实验性同种和异种移植小鼠模型中，进一步研究了该ASP在结直肠癌进展方面的定性和定量稳定性。建立了一个复杂的临床前实验装置，分别测试肿瘤进展的不同步骤和肿瘤微环境的作用，重点是“CD44”在这一过程中的作用。我们设法提出了一种结直肠癌特异性CD44 ASP，在整个原发性肿瘤形成和转移进展过程中，该ASP与细胞系保持不变。此外，我们报告了一个独特的名册，所有表达的CD44变异异构体特征的结直肠癌。最后，在可变外显子v3和v6的定量评估中，发现较高的共表达水平是转移性强的肿瘤细胞的特征。特定的CD44变体同种型似乎通过肿瘤微环境驱动的v3和v6表达的转变充当“转移基因”。然而，这种功能可能只影响少数肿瘤亚克隆。这一事实和可能含有v3和v6结构域的大量不同CD44剪接变体可以解释关于CD44变体功能评估的临床研究的不一致性，以及减少使用CD44变体用于预测目的的机会。
CD44 is considered as ‘a’ metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing. However, little consideration is given to the above in the literature of colorectal carcinomas as well as other tumour types, leading to confusion and contradictory results about its possible role in tumour progression. We compared the CD44 alternative splice pattern (ASP) of three genetically different human colorectal cancer cell lines (HT25, HT29, HCT116) using a series of PCR reactions and next- generation sequencing method, as well as identified a colorectal adenocarcinoma specific CD44 ASP. This ASP was further investigated in terms of its qualitative and quantitative stability in our experimental iso- and xenograft mouse models for colorectal cancer progression. A complex preclinical experimental set-up was established to separately test the different steps of tumour progression and the role of tumour microenvironment, respectively, focusing on the role of ‘CD44’ in this process. We managed to present a colorectal cancer-specific CD44 ASP, which remained unchanged from cell lines throughout primary tumour formation and metastatic progression. Furthermore, we report a unique roster of all expressed CD44 variant isoforms characteristic to colorectal cancer. Finally, on quantitative assessment of the variable exons v3 and v6, higher co-expression levels were found to be characteristic to metastatically potent tumour cells. Particular CD44 variant isoforms seem to act as “metastasis genes” via tumour microenvironment-driven shifts in v3 and v6 expressions. However, this function may just affect a minority of tumour subclones. This fact and the huge potential number of different CD44 splice variants that can contain v3 and v6 domains can explain incoherence of clinical studies regarding functional asessment of CD44 variants, as well as diminish the chances of using CD44 variants for predictive purpose.
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DOI：
10.1186/bcr1673
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fillmore C;Kuperwasser C
通讯作者：
Kuperwasser C
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
5
作者：
Faleiro-Rodrigues, C;Lopes, C
通讯作者：
Lopes, C
影响因子：
5.7
作者：
Hao, Honglin;Muniz-Medina, Vanessa M.;Shields, Janiel M.
通讯作者：
Shields, Janiel M.
影响因子：
3.9
作者：
Asao, T;Nakamura, J;Kuwano, H
通讯作者：
Kuwano, H