c-FOS suppresses ovarian cancer progression by changing adhesion
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c-FOS suppresses ovarian cancer progression by changing adhesion. / Oliveira Ferrer, Leticia; Rößler, K; Haustein, V; Schröder, Christine; Wicklein, D; Maltseva, D; Khaustova, N; Samatov, T; Tonevitsky, A; Mahner, S; Jänicke, F; Schumacher, U; Milde-Langosch, K.
In: BRIT J CANCER, Vol. 110, No. 3, 04.02.2014, p. 753-63.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - c-FOS suppresses ovarian cancer progression by changing adhesion
AU - Oliveira Ferrer, Leticia
AU - Rößler, K
AU - Haustein, V
AU - Schröder, Christine
AU - Wicklein, D
AU - Maltseva, D
AU - Khaustova, N
AU - Samatov, T
AU - Tonevitsky, A
AU - Mahner, S
AU - Jänicke, F
AU - Schumacher, U
AU - Milde-Langosch, K
PY - 2014/2/4
Y1 - 2014/2/4
N2 - BACKGROUND: C-Fos was initially described as oncogene, but was associated with favourable prognosis in ovarian cancer (OvCa) patients. The molecular and functional aspects underlying this effect are still unknown.METHODS: Using stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration, invasion and apoptotic potential of c-FOS-overexpressing clones and controls were compared. Adherence to components of the extracellular matrix was analysed in static assays, and adhesion to E-selectin, endothelial and mesothelial cells in dynamic flow assays. The effect of c-FOS in vivo was studied after intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene expression were determined by microarray analysis.RESULTS: Tumour growth after injection into SCID mice was strongly delayed by c-FOS overexpression, with reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had only weak influence on proliferation and migration, but was strongly pro-apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV) and to E-selectin, endothelial and mesothelial cells was significantly reduced in c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion proteins and glycosylation enzymes in microarray analysis.CONCLUSION: In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces.
AB - BACKGROUND: C-Fos was initially described as oncogene, but was associated with favourable prognosis in ovarian cancer (OvCa) patients. The molecular and functional aspects underlying this effect are still unknown.METHODS: Using stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration, invasion and apoptotic potential of c-FOS-overexpressing clones and controls were compared. Adherence to components of the extracellular matrix was analysed in static assays, and adhesion to E-selectin, endothelial and mesothelial cells in dynamic flow assays. The effect of c-FOS in vivo was studied after intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene expression were determined by microarray analysis.RESULTS: Tumour growth after injection into SCID mice was strongly delayed by c-FOS overexpression, with reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had only weak influence on proliferation and migration, but was strongly pro-apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV) and to E-selectin, endothelial and mesothelial cells was significantly reduced in c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion proteins and glycosylation enzymes in microarray analysis.CONCLUSION: In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces.
KW - Animals
KW - Apoptosis
KW - Carcinogenesis
KW - Cell Adhesion
KW - Cell Line, Tumor
KW - Cell Movement
KW - Cell Proliferation
KW - Disease Progression
KW - Extracellular Matrix
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Mice
KW - Neoplasm Invasiveness
KW - Neoplastic Cells, Circulating
KW - Ovarian Neoplasms
KW - Proto-Oncogene Proteins c-fos
U2 - 10.1038/bjc.2013.774
DO - 10.1038/bjc.2013.774
M3 - SCORING: Journal article
C2 - 24322891
VL - 110
SP - 753
EP - 763
JO - BRIT J CANCER
JF - BRIT J CANCER
SN - 0007-0920
IS - 3
ER -