A novel role for junctional adhesion molecule-A in tumor proliferation: modulation by an anti-JAM-A monoclonal antibody.

Abstract

To identify new potential targets in oncology, functional approaches were developed using tumor cells as immunogens to select monoclonal antibodies targeting membrane receptors involved in cell proliferation. For that purpose cancer cells were injected into mice and resulting hybridomas were screened for their ability to inhibit cell proliferation in vitro. Based on this functional approach coupled to proteomic analysis, a monoclonal antibody specifically recognizing the human junctional adhesion molecule-A (JAM-A) was defined. Interestingly, compared to both normal and tumor tissues, we observed that JAM-A was mainly overexpressed on breast, lung and kidney tumor tissues. In vivo experiments demonstrated that injections of anti-JAM-A antibody resulted in a significant tumor growth inhibition of xenograft human tumors. Treatment with monoclonal antibody induced a decrease of the Ki67 expression and downregulated JAM-A levels. All together, our results show for the first time that JAM-A can interfere with tumor proliferation and suggest that JAM-A is a potential novel target in oncology. The results also demonstrate that a functional approach coupled to a robust proteomic analysis can be successful to identify new antibody target molecules that lead to promising new antibody-based therapies against cancers.

• Authors: Liliane Goetsch, Jean-François Haeuw, Charlotte Beau-Larvor, Alexandra Gonzalez, Laurence Zanna, Martine Malissard, Anne-Marie Lepecquet, Alain Robert, Christian Bailly, Matthieu Broussas, Nathalie Corvaia
• Journal: International journal of cancer (Int J Cancer) Vol. 132 Issue 6 Pg. 1463-74 (Mar 15 2013) ISSN: 1097-0215 [Electronic] United States
• PMID: 22886345 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 UICC.

Chemical References

• Antibodies, Monoclonal
• Cell Adhesion Molecules
• F11R protein, human
• Ki-67 Antigen
• Receptors, Cell Surface

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Cell Adhesion Molecules (analysis, antagonists & inhibitors, physiology)
• Cell Line, Tumor
• Cell Proliferation
• Female
• Humans
• Ki-67 Antigen (analysis)
• Mice
• Mice, Inbred BALB C
• Neoplasms (drug therapy, pathology)
• Receptors, Cell Surface (analysis, antagonists & inhibitors, physiology)