Adhesion of lymphocytes to bladder cancer cells: the role of the alpha(E)beta(7) integrin.
The alpha(E)beta(7)integrin (defined by CD103) is expressed by most intra-epithelial lymphocytes (IEL) but by fewer than 2% peripheral blood lymphocytes (PBL). An important ligand for this molecule is the epithelial cell adhesion molecule E-cadherin. Loss of E-cadherin is associated with increased invasion and metastasis in bladder cancer. This study examines the role of the alpha(E)beta(7)-E-cadherin interaction in lymphocyte targeting of bladder cancer cells. Lymphocytes were activated in vitro by mixed lymphocyte reaction (MLR) and CD103 was upregulated by treatment with transforming growth factor beta (TGFbeta). The CD103(+) lymphocytes were used in a flow cytometric adhesion assay with bladder cancer cell lines, differing in expression of E-cadherin and intercellular adhesion molecule-1 (ICAM-1). Antibody blockade was used to confirm the relative importance of CD103 and ICAM-1 to intercellular adhesion. Lymphocytes with upregulated CD103 compared to control lymphocytes showed enhanced adhesion to an E-cadherin expressing bladder cancer cell line ( P=0.0003). This increased adhesion could be abrogated by anti-CD103 adhesion blockade. For ICAM-1 expressing bladder cells, adhesion of lymphocytes could be markedly reduced using anti-ICAM-1 blockade. In conclusion, the upregulation of CD103 by lymphocytes increases adhesion to E-cadherin expressing bladder cancer targets. Loss of E-cadherin in bladder cancer progression may provide a mechanism both for increased invasion and effective immune evasion.
D015703:Antigens, CD / Q000096:biosynthesis; D002448:Cell Adhesion; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; D008024:Ligands; D011993:Recombinant Fusion Proteins; C091367:alpha E integrins; C070709:integrin alphaEbeta7; D018799:Intercellular Adhesion Molecule-1