期刊
CANCER GENE THERAPY
卷 13, 期 8, 页码 792-797出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cgt.7700947
关键词
CAR; gastrointestinal cancer; adenovirus-based therapies; cell adhesion; tumor differentiation
类别
资金
- NCI NIH HHS [P50CA89520, P30 CA82103] Funding Source: Medline
- NIDDK NIH HHS [P30 DK26743] Funding Source: Medline
- NIGMS NIH HHS [5R25GM59298-02] Funding Source: Medline
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.
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