Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation
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Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation. / Bondong, S; Kiefel, H; Hielscher, T; Zeimet, A G; Zeillinger, R; Pils, D; Schuster, E; Castillo-Tong, D C; Cadron, I; Vergote, I; Braicu, I; Sehouli, J; Mahner, S; Fogel, M; Altevogt, P.
in: ANN ONCOL, Jahrgang 23, Nr. 7, 01.07.2012, S. 1795-802.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation
AU - Bondong, S
AU - Kiefel, H
AU - Hielscher, T
AU - Zeimet, A G
AU - Zeillinger, R
AU - Pils, D
AU - Schuster, E
AU - Castillo-Tong, D C
AU - Cadron, I
AU - Vergote, I
AU - Braicu, I
AU - Sehouli, J
AU - Mahner, S
AU - Fogel, M
AU - Altevogt, P
PY - 2012/7/1
Y1 - 2012/7/1
N2 - BACKGROUND: Overexpression of L1-cell adhesion molecule (L1CAM) has been observed for various carcinomas and correlates with poor prognosis and late-stage disease. In vitro, L1CAM enhances proliferation, cell migration, adhesion and chemoresistance. We tested L1CAM and interleukin-1 beta (IL-1β) expression in tumor samples and ascitic fluid from ovarian carcinoma patients to examine its role as a prognostic marker.PATIENTS AND METHODS: We investigated tumor samples and ascitic fluid from 232 serous ovarian carcinoma patients for L1CAM by enzyme-linked immunosorbent assay. L1CAM expression was correlated with pathoclinical parameters and patients' outcome. IL-1β levels were measured in tumor cell lysates. Ovarian cancer cell lines were analyzed for the contribution of L1CAM to IL-1β production and nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation.RESULTS: We observed that L1CAM-expressing tumors show a highly invasive phenotype associated with restricted tumor resectability at primary debulking surgery and increased lymphogenic spread. Soluble L1CAM proved to be a marker for poor progression-free survival and chemoresistance. In ovarian carcinoma cell lines, the specific knock-down of L1CAM reduces IL-1β expression and NF-κB activity.CONCLUSIONS: L1CAM expression contributes to the invasive and metastatic phenotype of serous ovarian carcinoma. L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1β production and NF-κB activation.
AB - BACKGROUND: Overexpression of L1-cell adhesion molecule (L1CAM) has been observed for various carcinomas and correlates with poor prognosis and late-stage disease. In vitro, L1CAM enhances proliferation, cell migration, adhesion and chemoresistance. We tested L1CAM and interleukin-1 beta (IL-1β) expression in tumor samples and ascitic fluid from ovarian carcinoma patients to examine its role as a prognostic marker.PATIENTS AND METHODS: We investigated tumor samples and ascitic fluid from 232 serous ovarian carcinoma patients for L1CAM by enzyme-linked immunosorbent assay. L1CAM expression was correlated with pathoclinical parameters and patients' outcome. IL-1β levels were measured in tumor cell lysates. Ovarian cancer cell lines were analyzed for the contribution of L1CAM to IL-1β production and nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation.RESULTS: We observed that L1CAM-expressing tumors show a highly invasive phenotype associated with restricted tumor resectability at primary debulking surgery and increased lymphogenic spread. Soluble L1CAM proved to be a marker for poor progression-free survival and chemoresistance. In ovarian carcinoma cell lines, the specific knock-down of L1CAM reduces IL-1β expression and NF-κB activity.CONCLUSIONS: L1CAM expression contributes to the invasive and metastatic phenotype of serous ovarian carcinoma. L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1β production and NF-κB activation.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Ascitic Fluid
KW - Carcinoma
KW - Cell Line, Tumor
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Interleukin-1beta
KW - Kaplan-Meier Estimate
KW - Lymphatic Metastasis
KW - Middle Aged
KW - Multivariate Analysis
KW - NF-kappa B
KW - Neoplasm Invasiveness
KW - Neural Cell Adhesion Molecule L1
KW - Ovarian Neoplasms
KW - Phenotype
KW - Prognosis
KW - Young Adult
U2 - 10.1093/annonc/mdr568
DO - 10.1093/annonc/mdr568
M3 - SCORING: Journal article
C2 - 22228447
VL - 23
SP - 1795
EP - 1802
JO - ANN ONCOL
JF - ANN ONCOL
SN - 0923-7534
IS - 7
ER -