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Adhesion of lymphocytes to bladder cancer cells: The role of the αEβ7 integrin

Lookup NU author(s): Joanne Cresswell, Matthew Henry, Dr Helen Robertson, Professor David Neal, Professor John Kirby

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Abstract

The αEβ7 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 αEβ7-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 β (TGFβ). 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.


Publication metadata

Author(s): Henry MJ; Kirby JA; Cresswell J; Neal DE; Robertson H; Wong W

Publication type: Article

Publication status: Published

Journal: Cancer Immunology, Immunotherapy

Year: 2002

Volume: 51

Issue: 9

Pages: 483-491

ISSN (print): 0340-7004

ISSN (electronic): 1432-0851

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00262-002-0305-3

DOI: 10.1007/s00262-002-0305-3

PubMed id: 12357319


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