Adhesion of lymphocytes to bladder cancer cells:: the role of the αEβ7 integrin
Adhesion of lymphocytes to bladder cancer cells:: the role of the αEβ7 integrin
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DOI：
10.1007/s00262-002-0305-3
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发表时间：
2002-11-01
影响因子：
5.8
通讯作者：
Kirby, JA
中科院分区：
文献类型：
--
作者：
Cresswell, J;Wong, WK;Kirby, JA
α（E）β（7）整联蛋白（由CD 103定义）由大多数上皮内淋巴细胞（IEL）表达，但由少于2%的外周血淋巴细胞（PBL）表达。该分子的一个重要配体是上皮细胞粘附分子E-钙粘蛋白。E-钙粘蛋白的缺失与膀胱癌浸润和转移的增加有关。本研究检测了α（E）β（7）-E-钙粘蛋白相互作用在膀胱癌细胞淋巴细胞靶向中的作用。通过混合淋巴细胞反应（MLR）在体外活化淋巴细胞，并且通过用转化生长因子β（TGF β）处理上调CD 103。CD 103（+）淋巴细胞用于流式细胞术粘附测定与膀胱癌细胞系，不同的表达E-cadherin和细胞间粘附分子-1（ICAM-1）。使用抗体阻断来确认CD 103和ICAM-1对细胞间粘附的相对重要性。与对照淋巴细胞相比，CD 103上调的淋巴细胞显示出对表达E-钙粘蛋白的膀胱癌细胞系的粘附增强（P = 0.0003）。这种增加的粘附可以通过抗CD 103粘附阻断来消除。对于表达ICAM-1的膀胱细胞，使用抗ICAM-1阻断剂可以显著降低淋巴细胞的粘附。总之，淋巴细胞上调CD 103增加了对表达E-钙粘蛋白的膀胱癌靶标的粘附。膀胱癌进展中E-钙粘蛋白的缺失可能为增加侵袭和有效免疫逃避提供了机制。
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.