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CRIPTO-1 在皮肤黑色素瘤中的表达和功能作用。

Expression and functional role of CRIPTO-1 in cutaneous melanoma.

机构信息

Cell Biology and Biotherapy Unit, Research Department, INT-Fondazione Pascale, Naples 80131, Italy.

出版信息

Br J Cancer. 2011 Sep 27;105(7):1030-8. doi: 10.1038/bjc.2011.324. Epub 2011 Aug 23.

DOI:10.1038/bjc.2011.324
PMID:21863025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3185940/
Abstract

BACKGROUND

CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of human carcinoma of different histological origin. In this study we addressed the expression and the functional role of CR-1 in cutaneous melanoma.

METHODS

Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated modified Boyden chambers.

RESULTS

Expression of CR-1 protein and/or mRNA was found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21 melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased the invasive ability of melanoma cells that was prevented by treatment with either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530). Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive ability of melanoma cells. Finally, a close correlation was found in melanoma cells between the levels of expression of CR-1 and the effects of saracatinib on cell growth.

CONCLUSION

These data indicate that a significant fraction of cutaneous melanoma expresses CR-1 and that this growth factor is involved in the invasion and proliferation of melanoma cells.

摘要

背景

CRIPTO-1(CR-1)参与了不同组织来源的人类癌的发病机制和进展。在这项研究中,我们研究了 CR-1 在皮肤黑素瘤中的表达和功能作用。

方法

通过免疫组织化学、western blot 和/或流式细胞术评估黑素瘤和黑素瘤细胞系中 CR-1 蛋白的表达。通过实时 PCR 评估 mRNA 水平。在 Matrigel 包被的改良 Boyden 室中进行侵袭实验。

结果

在 37 例原发性人类皮肤黑素瘤中的 16 例和 21 例黑素瘤细胞系中的 12 例中发现了 CR-1 蛋白和/或 mRNA 的表达。重组 CR-1 蛋白在黑素瘤细胞中激活 c-Src,并且在较小程度上激活 Smad 信号。此外,CR-1 显著增加了黑素瘤细胞的侵袭能力,而 ALK4 抑制剂 SB-431542 或 c-Src 抑制剂 saracatinib(AZD0530)的处理则阻止了这种侵袭能力的增加。抗 CR-1 siRNAs 显著抑制了黑素瘤细胞的生长和侵袭能力。最后,在黑素瘤细胞中发现 CR-1 的表达水平与 saracatinib 对细胞生长的影响之间存在密切相关性。

结论

这些数据表明,相当一部分皮肤黑素瘤表达 CR-1,并且这种生长因子参与了黑素瘤细胞的侵袭和增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/9e09e8223c23/bjc2011324f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/98ef217184a7/bjc2011324f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/5c99d0dfc091/bjc2011324f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/bfc545cc356f/bjc2011324f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/251c4fa34133/bjc2011324f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/b684472805a9/bjc2011324f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/51cff6c54ce3/bjc2011324f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/9e09e8223c23/bjc2011324f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/98ef217184a7/bjc2011324f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/5c99d0dfc091/bjc2011324f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/bfc545cc356f/bjc2011324f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/251c4fa34133/bjc2011324f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/b684472805a9/bjc2011324f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/51cff6c54ce3/bjc2011324f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29c/3185940/9e09e8223c23/bjc2011324f7.jpg

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The EGFR Signaling Modulates in Mesenchymal Stem Cells the Expression of miRNAs Involved in the Interaction with Breast Cancer Cells.表皮生长因子受体(EGFR)信号传导调节间充质干细胞中参与与乳腺癌细胞相互作用的微小RNA(miRNA)的表达。
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