The homophilic binding of junctional adhesion molecule-C mediates tumor cell-endothelial cell interactions.

The junctional adhesion molecule C (JAM-C) was recently shown to undergo a heterophilic interaction with the leukocyte beta2 integrin Mac-1, thereby mediating interactions between vascular cells in inflammatory cell recruitment. Here, the homophilic interaction of JAM-C is presented and functionally characterized to mediate tumor cell-endothelial cell interactions. Recombinant soluble JAM-C in fluid phase bound to immobilized JAM-C as assessed in a purified system; moreover, JAM-C-transfected Chinese hamster ovary (CHO) cells adhered to immobilized JAM-C. The homophilic interaction of JAM-C was mediated by the isolated amino-terminal Ig domain (D1), but not the carboxyl-terminal Ig domain (D2), of the molecule. Dimerization of JAM-A is dependent on the sequence RVE in the amino-terminal Ig domain. This motif is conserved in JAM-C (Arg64-Ile65-Glu66), and a single amino acid mutation in this motif (E66R) abolished the homophilic interaction of JAM-C. The lung carcinoma cell line NCI-H522 was found to express JAM-C. NCI-H522 cells adhered to immobilized JAM-C, as well as to JAM-C-transfected CHO cells, but not to mock-transfected CHO cells or to CHO cells transfected with the JAM-C mutant (E66R). Adhesion of NCI-H522 cells to JAM-C protein or JAM-C-transfected CHO cells was abolished in the presence of soluble JAM-C or the isolated D1. Furthermore, the adhesion of NCI-H522 cells to endothelial cells was significantly blocked by soluble JAM-C or the isolated D1. Thus, JAM-C undergoes a homophilic interaction via the Arg64-Ile65-Glu66 motif on the membrane-distal Ig domain of the molecule. The homophilic interaction of JAM-C can mediate tumor cell-endothelial cell interactions and may thereby be involved in the process of tumor cell metastasis.
AuthorsSentot Santoso, Valeria V Orlova, Kaimei Song, Ulrich J Sachs, Cornelia L Andrei-Selmer, Triantafyllos Chavakis
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 280 Issue 43 Pg. 36326-33 (Oct 28 2005) ISSN: 0021-9258 [Print] United States
PMID16118203 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cell Adhesion Molecules
  • Immunoglobulin G
  • Immunoglobulins
  • JAM3 protein, human
  • Membrane Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Amino Acid Motifs
  • Animals
  • CHO Cells
  • Cell Adhesion
  • Cell Adhesion Molecules (chemistry, physiology)
  • Cell Line, Tumor
  • Cells, Cultured
  • Cricetinae
  • Dimerization
  • Dose-Response Relationship, Drug
  • Endothelial Cells (cytology)
  • Endothelium, Vascular (cytology)
  • Escherichia coli (metabolism)
  • Flow Cytometry
  • Humans
  • Immunoglobulin G (chemistry)
  • Immunoglobulins (chemistry, physiology)
  • Membrane Proteins (chemistry, physiology)
  • Microscopy, Fluorescence
  • Mutation
  • Neoplasm Metastasis
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins (chemistry)
  • Recombinant Proteins (chemistry)
  • Surface Plasmon Resonance
  • Transfection
  • Umbilical Veins (cytology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: