L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells.
OBJECTIVE
Apoptosis resistance is a hallmark of cancer progression, a phenomenon frequently observed in ovarian carcinoma. We reported previously, that L1 adhesion molecule (CD171) is overexpressed in ovarian and endometrial carcinomas and that L1 expression is a predictor of poor outcome. We investigated a possible role of L1 in apoptosis resistance.


METHODS
We used L1 transfectants and ovarian carcinoma cell lines and induced apoptosis by different stimuli such as C2-ceramide, staurosporine, cisplatin or hypoxia.


RESULTS
We found that cells expressing L1 are more resistant against apoptosis. In HEK293 cells, L1-expresssion leads to a sustained ERK, FAK and PAK phosphorylation. Soluble L1 only partially rescued HEK293 cells from apoptosis. Treatment with apoptotic stimuli upregulated the anti-apoptotic molecule Bcl-2 to a greater extend in HEK293 cells expressing L1. In the ovarian carcinoma cell line OVMz, the depletion of L1 by RNA interference sensitized cells for apoptosis induction. No changes in activation of ERK or FAK were observed after L1 knockdown. The selection of m130 ovarian carcinoma or SW707 colon carcinoma cells with cisplatin leads to upregulated expression of L1.


CONCLUSIONS
Our results suggest a link between L1 expression and chemoresistance of ovarian carcinomas. Upregulation of L1 after cisplatin treatment might indicate a more malignant tumor phenotype given the established role of L1 in cell motility and invasion.
Stoeck
Alexander
A
Tumor Immunology Programme, D010, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Gast
Daniela
D
Sanderson
Michael P
MP
Issa
Yasmin
Y
Gutwein
Paul
P
Altevogt
Peter
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection
C064769:N-acetylsphingosine; D039842:Neural Cell Adhesion Molecule L1; D019311:Staurosporine; D013110:Sphingosine; D002945:Cisplatin