Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers.
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.
Wang
Jianbo
J
Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Day
Ryan
R
Dong
Yiyu
Y
Weintraub
Steven J
SJ
Michel
Loren
L
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D015316:Genetic Therapy; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D009857:Oncogenes / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D014162:Transfection; D015854:Up-Regulation
D000906:Antibodies; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human