CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
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CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells. / Wicklein, Daniel; Otto, Benjamin; Suling, Anna; Elies, Eva; Lüers, Georg; Lange, Tobias; Feldhaus, Susanne; Maar, Hanna; Schröder-Schwarz, Jennifer; Brunner, Georg; Wagener, Christoph; Schumacher, Udo.
In: SCI REP-UK, Vol. 8, 08.08.2018, p. 11893.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
AU - Wicklein, Daniel
AU - Otto, Benjamin
AU - Suling, Anna
AU - Elies, Eva
AU - Lüers, Georg
AU - Lange, Tobias
AU - Feldhaus, Susanne
AU - Maar, Hanna
AU - Schröder-Schwarz, Jennifer
AU - Brunner, Georg
AU - Wagener, Christoph
AU - Schumacher, Udo
PY - 2018/8/8
Y1 - 2018/8/8
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/s41598-018-30338-4
DO - 10.1038/s41598-018-30338-4
M3 - SCORING: Journal article
C2 - 30089785
VL - 8
SP - 11893
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -
