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

✍ Scribed by Syed A. Ahmad; Wenbiao Liu; Young D. Jung; Fan Fan; Niels Reinmuth; Corazon D. Bucana; Lee M. Ellis

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 500 KB
• Volume: 92
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(20010901)92:5<1138::aid-cncr1431>3.0.co;2-l

✦ Synopsis

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.