Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma. A possible mechanism for the initiation of angiogenesis

Cancer. 2001 Sep 1;92(5):1138-43. doi: 10.1002/1097-0142(20010901)92:5<1138::aid-cncr1431>3.0.co;2-l.


Background: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are important regulators of endothelial cell (EC) survival. Current models suggest that an increase in Ang-2 expression in ECs leads to the initiation of angiogenesis. The authors hypothesized that the imbalance of Ang-1 and Ang-2 activities in colon carcinoma leads to a net gain in Ang-2 function.

Methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses and immunofluorescent double-staining were performed to examine human colon carcinoma cell lines, surgical specimens, normal mucosa, and liver metastases for the expression of Ang-1 and Ang-2.

Results: RT-PCR analyses revealed that 7 of 18 colon carcinoma cell lines expressed Ang-1, and 14 of 18 colon carcinoma cell lines expressed Ang-2 (P < 0.05). Of the surgical specimens from patients with colon carcinoma, 6 of 11 specimens expressed Ang-1, and 11 of 11 specimens expressed Ang-2 (P < 0.05). However, Ang-1 and Ang-2 were expressed with relative equal frequency in normal mucosa (P = 0.62). Immunofluorescent staining (n = 20 specimens) revealed the presence of Ang-2 protein in normal mucosa and tumor epithelium, but Ang-1 was expressed only in normal mucosa. A similar pattern was found for hepatic colorectal metastases. Double staining for Ang-1 or Ang-2 and cytokeratin-22 (an epithelial marker) demonstrated that Ang-1 was produced by uninvolved, normal colonic epithelium, whereas Ang-2 was produced by normal and malignant colonic epithelium.

Conclusions: In patients with colon carcinoma, Ang-2 is expressed ubiquitously in tumor epithelium, whereas expression of Ang-1 in tumor epithelium is rare. The net gain of Ang-2 activity is possibly an initiating factor for tumor angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Angiopoietin-1
  • Angiopoietin-2
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Keratins / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Neovascularization, Pathologic / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • ANGPT1 protein, human
  • Actins
  • Angiopoietin-1
  • Angiopoietin-2
  • Membrane Glycoproteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proteins
  • RNA, Messenger
  • Keratins