L1 on ovarian carcinoma cells is a binding partner for Neuropilin-1 on mesothelial cells.
The progression of ovarian cancer is driven by a variety of cellular factors that are incompletely understood. Binding of tumor cells to normal cells and to soluble factors influence tumor growth, angiogenesis and the stimulation of vascular permeability leading to ascites production. L1 adhesion molecule is overexpressed in ovarian carcinoma and is associated with bad prognosis. One receptor for L1 is Neuropilin-1 (NRP-1) that is also known as a receptor for VEGF(165). In the nervous system a complex of NRP-1 and L1 transmits signals by the neurorepellant Sem3A that is critical for the control of neurite outgrowth. NRP-1 has also been detected in human carcinomas but its function remains unknown. Here, we have examined NRP-1 expression in ovarian carcinoma cell lines and tissue. We report that little NRP-1 protein was detected in primary ovarian carcinoma tissues or established cell lines although mRNA for soluble and transmembrane NRP-1 were detected by RT-PCR. Instead, we observed strong expression of NRP-1 in mesothelial cells, which form the lining of the peritoneum. NRP-1 could serve as an isolation marker for primary mesothelial cells present in ascites fluid. We demonstrate that ovarian cancer cells expressing L1 can bind to NRP-1 overexpressing cells and mesothelial cells. Likewise, soluble L1 isolated from ascites of patients or produced as a fusion protein could bind to NRP-1 overexpressing cells and a direct interaction was demonstrated at the protein level. These findings suggest that L1 can support the binding of ovarian carcinoma cells to mesothelial cells via NRP-1. The L1-NRP-1 binding pathway could contribute to the growth of ovarian carcinomas and to reciprocal signalling between mesothelial cells and tumors.
Stoeck
Alexander
A
Tumor Immunology Programme, German Cancer Research Center, D010, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Schlich
Sabine
S
Issa
Yasmin
Y
Gschwend
Verena
V
Wenger
Till
T
Herr
Ingrid
I
Marmé
Alexander
A
Bourbie
Sarah
S
Altevogt
Peter
P
Gutwein
Paul
P
D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D006801:Humans; D008856:Microscopy, Fluorescence; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D039942:Neuropilin-1 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D039842:Neural Cell Adhesion Molecule L1; D039942:Neuropilin-1