Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation
Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation
复制标题
DOI：
10.1038/sj.cgt.7700947
复制
发表时间：
2006-08-01
影响因子：
6.4
通讯作者：
Ferrell, L.
中科院分区：
文献类型：
--
作者：
Korn, W. M.;Macal, M.;Ferrell, L.
改良腺病毒为胃肠道肿瘤的治疗提供了一条新途径。然而，在许多情况下，它们被细胞摄取需要腺病毒的主要受体，柯萨奇病毒和腺病毒受体(CAR)。因此，CAR表达的缺乏是肿瘤细胞对这种治疗产生内在耐药的潜在原因。为了评估这一点，我们研究了CAR蛋白在正常和恶性胃肠道组织中的定位。在正常组织中，CAR主要集中在细胞与细胞相互作用的部位，尤其是细胞的顶侧表面。在胆汁和胰管周围的表达尤其强烈，这与CAR作为紧密连接蛋白的生理功能一致。在胃肠道恶性肿瘤(食道癌、胰腺癌、结直肠癌和肝癌)中，该受体的表达差异很大。在许多样本中，细胞-细胞交界处CAR表达的缺失很明显。CAR表达与组织学分级显著相关，中至低分化肿瘤最常表现为CAR表达缺失或减少。这些数据表明，CAR在胃肠道恶性肿瘤中的表达经常发生改变，这可能会减低腺病毒为基础的治疗的疗效。
Modified adenoviruses represent a new approach to treatment of gastrointestinal cancer. However, their uptake by cells in many cases requires the major receptor for adenoviruses, the coxsackievirus and adenovirus receptor ( CAR). Thus, lack of CAR expression is a potential cause of intrinsic resistance of tumor cells to this type of treatment. To evaluate this, we studied the localization of CAR protein in normal and malignant gastrointestinal tissues. In normal tissues, CAR was concentrated at sites of cell-cell interaction, in particular at the apico-lateral cellular surface. Expression was particularly strong around bile and pancreatic ducts, which is in agreement with CAR's physiological function as a tight-junction protein. In GI malignancies (esophageal, pancreatic, colorectal and liver cancer), expression of the receptor varied substantially. Loss of CAR expression at cell-cell junction was evident in many samples. A significant correlation between CAR expression and histological grade was found, with moderately to poorly differentiated tumors most frequently demonstrating loss or reduction of CAR expression. These data indicate that CAR expression is frequently altered in gastrointestinal malignancy, potentially reducing the efficacy of adenovirus-based therapies.