L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.
BACKGROUND/AIMS: 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 ther...
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doaj-a997d1336b7c45f2a76254da092a42032020-11-24T21:50:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8251210.1371/journal.pone.0082512L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.Cássia G T SilveiraDominique FinasPeter HunoldFrank KösterKatharina StroscheinGeraldine O CannyGerhard MoldenhauerPeter AltevogtAchim RodyDaniela HornungBACKGROUND/AIMS: 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. METHODS AND RESULTS: 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<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). CONCLUSIONS: Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models.http://europepmc.org/articles/PMC3853202?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cássia G T Silveira Dominique Finas Peter Hunold Frank Köster Katharina Stroschein Geraldine O Canny Gerhard Moldenhauer Peter Altevogt Achim Rody Daniela Hornung |
spellingShingle |
Cássia G T Silveira Dominique Finas Peter Hunold Frank Köster Katharina Stroschein Geraldine O Canny Gerhard Moldenhauer Peter Altevogt Achim Rody Daniela Hornung L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. PLoS ONE |
author_facet |
Cássia G T Silveira Dominique Finas Peter Hunold Frank Köster Katharina Stroschein Geraldine O Canny Gerhard Moldenhauer Peter Altevogt Achim Rody Daniela Hornung |
author_sort |
Cássia G T Silveira |
title |
L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. |
title_short |
L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. |
title_full |
L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. |
title_fullStr |
L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. |
title_full_unstemmed |
L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. |
title_sort |
l1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
BACKGROUND/AIMS: 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. METHODS AND RESULTS: 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<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). CONCLUSIONS: Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models. |
url |
http://europepmc.org/articles/PMC3853202?pdf=render |
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