Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation

W. M. Korn, M. Macal, C. Christian, M. D. Lacher, A. McMillan, Katherine A Rauen, R. S. Warren, L. Ferrell

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)792-797
Number of pages6
JournalCancer Gene Therapy
Volume13
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Gastrointestinal Neoplasms
Enterovirus
Neoplasms
Adenoviridae
Tight Junction Proteins
adenovirus receptor
Intercellular Junctions
Pancreatic Ducts
Liver Neoplasms
Esophageal Neoplasms
Bile Ducts
Pancreatic Neoplasms
Cell Communication
Colorectal Neoplasms

Keywords

  • Adenovirus-based therapies
  • CAR
  • Cell adhesion
  • Gastrointestinal cancer
  • Tumor differentiation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation. / Korn, W. M.; Macal, M.; Christian, C.; Lacher, M. D.; McMillan, A.; Rauen, Katherine A; Warren, R. S.; Ferrell, L.

In: Cancer Gene Therapy, Vol. 13, No. 8, 08.2006, p. 792-797.

Research output: Contribution to journalArticle

Korn, W. M. ; Macal, M. ; Christian, C. ; Lacher, M. D. ; McMillan, A. ; Rauen, Katherine A ; Warren, R. S. ; Ferrell, L. / Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation. In: Cancer Gene Therapy. 2006 ; Vol. 13, No. 8. pp. 792-797.
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