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

Abstract
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
Topics
  • 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)

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