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 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.
Ahmad
S A
SA
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Liu
W
W
Jung
Y D
YD
Fan
F
F
Reinmuth
N
N
Bucana
C D
CD
Ellis
L M
LM
D000199:Actins / Q000378:metabolism; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C467630:ANGPT1 protein, human; D000199:Actins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011506:Proteins; D012333:RNA, Messenger; D007633:Keratins