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

BACKGROUND. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are important regulators of endothelial cell (EC survival. Current models suggest that a ll increase in Ang-2 expression in ECs leads to the initiation of angiogene sis. The authors hypothesized that the imbalance of Ang-1 and Ang-2 activit ies 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 metasta ses for the expression of Ang-1 and Ang-2. RESULTS. RT-PCR analyses revealed that 7 of 18 colon carcinoma cell lines e xpressed 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-I and Ang-2 were expressed with relative equal frequenc y in normal mucosa (P = 0.62). Immuno fluorescent staining (n = 20 specimen s) revealed the presence of Ang-2 protein in normal mucosa and tumor epithe lium, 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 prod uced by uninvolved, normal colonic epithelium, whereas Ang-2 was produced b y normal and malignant colonic epithelium. CONCLUSIONS. in patients with colon carcinoma, Ang-2 is expressed ubiquitou sly 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 turner angiogenesis. (C) 2001 American Cancer Society.