Cooperative expression of junctional adhesion molecule-C and -B supports growth and invasion of glioma.
Brain invasion is a biological hallmark of glioma that contributes to its aggressiveness and limits the potential of surgery and irradiation. Deregulated expression of adhesion molecules on glioma cells is thought to contribute to this process. Junctional adhesion molecules (JAMs) include several IgSF members involved in leukocyte trafficking, angiogenesis, and cell polarity. They are expressed mainly by endothelial cells, white blood cells, and platelets. Here, we report JAM-C expression by human gliomas, but not by their normal cellular counterpart. This expression correlates with the expression of genes involved in cytoskeleton remodeling and cell migration. These genes, identified by a transcriptomic approach, include poliovirus receptor and cystein-rich 61, both known to promote glioma invasion, as well as actin filament associated protein, a c-Src binding partner. Gliomas also aberrantly express JAM-B, a high affinity JAM-C ligand. Their interaction activates the c-Src proto-oncogene, a central upstream molecule in the pathways regulating cell migration and invasion. In the tumor microenvironment, this co-expression may thus promote glioma invasion through paracrine stimuli from both tumor cells and endothelial cells. Accordingly, JAM-C/B blocking antibodies impair in vivo glioma growth and invasion, highlighting the potential of JAM-C and JAM-B as new targets for the treatment of human gliomas.
Service of Oncology, Laboratory of Tumor Immunology, Geneva University Hospitals and University of Geneva, 1211 Geneva 14, Switzerland.
Mirna
M
Tenan
Michel
M
Aurrand-Lions
Valerie
V
Widmer
Alessandro
A
Alimenti
Karim
K
Burkhardt
François
F
Lazeyras
Marie-Claude
MC
Belkouch
Philippe
P
Hammel
Paul R
PR
Walker
Michel A
MA
Duchosal
Beat A
BA
Imhof
Pierre-Yves
PY
Dietrich
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000379:methods / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000090063:Proto-Oncogene Mas; D062765:Junctional Adhesion Molecule B
D000906:Antibodies; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D000090063:Proto-Oncogene Mas; C448000:JAM3 protein, human; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B; C000715470:MAS1 protein, human