title: Investigation of the role of beta 1 integrins in cell-cell adhesion.
abstract: Various beta 1 integrins (VLA-2, VLA-3, VLA-4) have been suggested to bind directly to themselves or to each other, thus mediating cell-cell adhesion. Here we expressed the human alpha 2 and alpha 3 subunits in three different cell lines (human erythroleukemia K562, human rhabdomyosarcoma RD and Chinese hamster ovary CHO cells). Although cell surface alpha 2 beta 1 and alpha 3 beta 1 in the transfectants mediated adhesion to matrix ligands (collagen or laminin 5, respectively), in no case did we observe enhanced cell-cell adhesion. In the presence of a range of different divalent cation concentrations, stimulatory anti-beta 1 antibodies or anti-alpha 3 antibodies, VLA-2 and VLA-3 still did not appear to interact directly, through either heterophilic (i.e. VLA-3/VLA-2) or homophilic (i.e. VLA-3/VLA-3) mechanisms, to mediate cell-cell adhesion. Furthermore, in some but not all alpha 3 transfectants we observed an unexpected decrease in cell-cell adhesion, suggesting a novel anti-adhesive function. This inhibitory effect was not observed for alpha 2 transfection nor when the alpha 3 cytoplasmic tail was exchanged with that of another integrin alpha subunit. Finally, no evidence for VLA-4/VLA-4 mediated cell-cell adhesion was observed using alpha 4-transfected K562 and CHO cells. In conclusion, using many different combinations of cell lines, we found that cell-cell adhesion mediated by direct integrin/integrin interaction is not a widespread phenomenon, and is not observable in standard cell-cell adhesion assays. Furthermore, in some cell combinations, alpha 3 expression may actually cause diminished cell-cell adhesion.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Weitzman
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: M E
authors.initials: ME
authors.lastname: Hemler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D016466:CHO Cells / Q000166:cytology; D002294:Carcinoma, Squamous Cell; D002352:Carrier Proteins / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D006224:Cricetinae; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D005354:Fibrosarcoma; D018922:HL-60 Cells / Q000166:cytology; D006801:Humans; D039201:Integrin alpha3beta1; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000187:drug effects / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D038981:Receptors, Collagen; D017474:Receptors, Laminin / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D012208:Rhabdomyosarcoma; D014162:Transfection / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology
chemical_list: D002352:Carrier Proteins; D039201:Integrin alpha3beta1; D019012:Integrin beta1; D016023:Integrins; D038981:Receptors, Collagen; D017474:Receptors, Laminin; D016029:Receptors, Very Late Antigen