L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach

• Published in: PloS one 2013-12, Vol.8 (12), p.e82512-e82512
• Main Authors: Silveira, Cássia G T, Finas, Dominique, Hunold, Peter, Köster, Frank, Stroschein, Katharina, Canny, Geraldine O, Moldenhauer, Gerhard, Altevogt, Peter, Rody, Achim, Hornung, Daniela
• Format: Article
• Language: English
• Subjects: Adhesion; Adult; Animal models; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacology; Autografts; Axonogenesis; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell adhesion molecules; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Disease Models, Animal; Endometriosis; Endometriosis - drug therapy; Endometriosis - metabolism; Endometriosis - pathology; Endometrium; Female; Glycoproteins; Health aspects; Humans; Immunoglobulin G; Immunohistochemistry; Implantation; In vivo methods and tests; Kinases; Lesions; Magnetic resonance; Magnetic resonance imaging; Mice; Molecular modelling; Monoclonal antibodies; Nerves; Neural cell adhesion molecule; Neural Cell Adhesion Molecule L1 - antagonists & inhibitors; Neural Cell Adhesion Molecule L1 - metabolism; Neurofilament Proteins - metabolism; Peritoneum; Proliferating cell nuclear antigen; Rodents; Stromal cells; Surgery; Surgical implants; Transplantation; Tumors; Womens health; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082512

The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb) to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth. Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21) mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P