CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells

被引：23

作者：

Wicklein, Daniel ^{[1
]}

Otto, Benjamin ^{[2
,3
]}

Suling, Anna ^{[4
]}

Elies, Eva ^{[1
]}

Lueers, Georg ^{[1
]}

Lange, Tobias ^{[1
]}

Feldhaus, Susanne ^{[1
]}

Maar, Hanna ^{[1
]}

Schroeder-Schwarz, Jennifer ^{[1
]}

Brunner, Georg ^{[5
,7
]}

Wagener, Christoph ^{[6
]}

Schumacher, Udo ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr, Inst Anat & Expt Morphol, Hamburg, Germany

[2] Eppendorf AG, Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany

[5] Fachklin Hornheide, Dept Canc Res, Munster, Germany

[6] Univ Med Ctr Hamburg Eppendorf, Ctr Diagnost, Hamburg, Germany

[7] NeraCare GmbH, Bonen, Germany

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

BILIARY GLYCOPROTEIN; ADHESION MOLECULE-1; MALIGNANT-MELANOMA; EXPRESSION; NORMALIZATION; SURVIVAL; INVASION; GROWTH;

D O I：

10.1038/s41598-018-30338-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metastasis was quantified histologically. Results and identified markers were verified using tissue samples of over 100 melanoma patients. Knockdown of CEACAM1 prolonged the animals' survival by significantly reducing subcutaneous growth of MeWo tumors and spontaneous lung metastasis. Microarray analysis revealed a strong influence of CEACAM1 knockdown on the network of EMT associated genes in the xenograft tumors (e.g. downregulation of BRAF, FOSL1, NRAS and TWIST). IGFBP7 and Latexin (highest up-and downregulated expression in microarray analysis) were found to be associated with longer and shorter survival, respectively, of melanoma patients. High FOSL1 and altered TWIST1 expression were found to be correlated with shortened survival in the cohort of melanoma patients. After a stepwise selection procedure combining above markers, multivariate analysis revealed IGFBP7, Latexin and altered TWIST to be prognostic markers for death. CEACAM1 could be a target for melanoma therapy as an alternative to (or in combination with) immune checkpoint and BRAF inhibitors.

引用

页数：13

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