Differential stromal and epithelial localization of cyclooxygenase-2 (COX-2) during colorectal tumorigenesis.
The purpose of the following study is to describe the localization of COX-2 protein and COX-2 mRNA during human colorectal tumorigenesis and to identify potential cellular targets for COX-2 inhibition in chemopreventive strategies. Immunohistochemistry with digital image analysis was used to determine COX-2 protein expression in histologic sections containing synchronous normal colorectal mucosa, adenomas and carcinomas, from 17 previously untreated patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected samples from the same histologies. The stromal compartment in normal colorectal mucosa and adenomas showed higher levels of COX-2 protein expression compared to colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was significantly increased only after development of the invasive phenotype (p < .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that within the epithelium for colorectal adenomas and carcinomas. In conclusion, stromal COX-2 may be the target for chemopreventive agents in the early stages of colorectal carcinogenesis.
Arnoletti
J P
JP
Dept. of Surgery, Section of Surgical Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Upson
J
J
Babb
J S
JS
Bellacosa
A
A
Watson
J C
JC
D000236:Adenoma / Q000378:metabolism; D015139:Blotting, Southern; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D017154:Stromal Cells / Q000201:enzymology*; D013997:Time Factors
D018076:DNA, Complementary; D012333:RNA, Messenger; D012313:RNA