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Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers.

Authors
  • Wang, Jianbo
  • Day, Ryan
  • Dong, Yiyu
  • Weintraub, Steven J
  • Michel, Loren
Type
Published Article
Journal
Molecular cancer therapeutics
Publication Date
Feb 01, 2008
Volume
7
Issue
2
Pages
280–285
Identifiers
DOI: 10.1158/1535-7163.MCT-07-2003
PMID: 18281513
Source
Medline
License
Unknown

Abstract

The cell surface protein Trop-2 is highly expressed in a wide variety of epithelial cancers. In contrast, there is little or no expression of Trop-2 in adult somatic tissue. Because it is a cell surface protein that is selectively expressed in tumor cells, Trop-2 is a potential therapeutic target. However, whether Trop-2 is actively involved in tumorigenesis and whether its targeting for treatment would be effective have not been examined. Here, we show that Trop-2 expression is necessary for tumorigenesis and invasiveness of colon cancer cells, as both are inhibited when Trop-2 expression is suppressed by RNA interference. Conversely, ectopic expression of Trop-2 in colon cancer cells enhances their capacity for anchorage-independent growth and ectopic expression of Trop-2 in NIH3T3 cells is sufficient to promote both anchorage-independent growth and tumorigenesis. Importantly, we show that an antibody against the extracellular domain of Trop-2 reduces tumor cell invasiveness. Therefore, we have identified Trop-2 as an oncogene that has potential as a therapeutic target. Given the restricted expression of Trop-2 in normal tissue, anti-Trop-2 therapeutics would be predicted to have limited toxicity.

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