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Published on: March 30, 2018
A novel role for junctional adhesion molecule-A in tumor proliferation: modulation by an anti-JAM-A monoclonal
Liliane Goetsch1, Jean-François Haeuw, Charlotte Beau-Larvor
1Institut de Recherche Pierre Fabre, Center d'Immunologie Pierre Fabre, 74160 Saint Julien en Genevois, France. liliane.goetsch@pierre-fabre.com
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.
Insights
Researchers identified junctional adhesion molecule-A (JAM-A) as a novel oncology target. Anti-JAM-A antibodies significantly inhibited tumor growth, suggesting JAM-A as a promising target for new cancer therapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Identifying novel molecular targets is crucial for advancing cancer therapy.
- Monoclonal antibodies offer targeted therapeutic strategies against cancer cells.
Purpose of the Study:
- To discover new targets for oncology by developing functional approaches using tumor cells.
- To generate monoclonal antibodies against membrane receptors involved in cancer cell proliferation.
Main Methods:
- Utilized tumor cells as immunogens in mice to select for hybridomas.
- Screened hybridomas for their ability to inhibit cancer cell proliferation in vitro.
- Employed proteomic analysis to identify antibody targets, specifically junctional adhesion molecule-A (JAM-A).
Main Results:
- Defined a monoclonal antibody targeting human junctional adhesion molecule-A (JAM-A).
- Observed significant JAM-A overexpression in breast, lung, and kidney tumor tissues compared to normal tissues.
- Demonstrated significant inhibition of xenograft human tumor growth in vivo using anti-JAM-A antibodies.
- Observed decreased Ki67 expression and downregulated JAM-A levels following antibody treatment.
Conclusions:
- Junctional adhesion molecule-A (JAM-A) plays a role in tumor proliferation and represents a potential novel target in oncology.
- A functional approach combined with proteomic analysis is effective for identifying new antibody targets.
- The findings support the development of promising new antibody-based cancer therapies targeting JAM-A.
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