L1 augments cell migration and tumor growth but not beta3 integrin expression in ovarian carcinomas.
L1 is a neural cell adhesion molecule involved in cell migration, axon growth and guidance. Recent data have shown that L1 is overexpressed in ovarian and endometrial tumors and is associated with bad prognosis. How L1 promotes tumor progression is presently unknown. Here we show that L1 expression is predominantly confined to the invasive front of ovarian carcinomas. Overexpression of L1 in carcinoma cell lines by adenovirus-mediated gene transfer enhanced the haptotactic cell migration on extracellular matrix proteins. Expression of L1 augmented tumor growth of carcinomas xenografted in nonobese diabetic/severe combined immunodeficient mice (NOD/SCID). A recent report has demonstrated L1-dependent upregulation of beta3 integrin involving activation of the extracellular signal-regulated kinase (erk) pathway. We find that L1 and beta3 integrin are not coexpressed in ovarian carcinoma tissues. Overexpression of L1 did not upregulate beta3 integrin in ovarian carcinoma cell lines but could do so in HEK293 cells. Our results suggest that L1 could drive progression by enhancing cell migration and tumor growth but that L1 dependent and erk-regulated gene expression requires cell-type specific elements.
Gast
Daniela
D
Tumor Immunology Programme, D010, German Cancer Research Center, Heidelberg, Germany.
Riedle
Svenja
S
Riedle
Svenja
S
Schabath
Heidi
H
Schlich
Sabine
S
Schneider
Annette
A
Issa
Yasmin
Y
Stoeck
Alexander
A
Fogel
Mina
M
Joumaa
Safwan
S
Wenger
Till
T
Herr
Ingrid
I
Gutwein
Paul
P
Altevogt
Peter
P
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D007668:Kidney; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous
D039661:Integrin beta3; D039842:Neural Cell Adhesion Molecule L1; D034741:RNA, Small Interfering