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

Syed A. Ahmad, Wenbiao Liu, Young D. Jung, Fan Fan, Niels Reinmuth, Corazon D. Bucana, Lee M. Ellis

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1138-1143
Number of pages6
JournalCancer
Volume92
Issue number5
DOIs
StatePublished - Sep 1 2001

Keywords

  • Angiogenesis
  • Angiopoietin
  • Apoptosis
  • Endothelial cells
  • Tie-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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