Expression patterns of endothelin-1 and its receptors in colorectal cancer.
OBJECTIVE
Endothelin-1 (ET-1), a potent vasoconstricting peptide, plays an important role in carcinogenesis. Previous in vitro studies have shown that colorectal cancer cells produce ET-1.


METHODS
ET-1 and its receptors ET-A (ET(A) R) and ET-B (ET(B) R) were analyzed in colorectal cancer cell lines and tumors by Western blot and immunohistochemistry. Also, ET-1 levels were measured by ELISA in blood samples collected before and after tumor resection.


RESULTS
ET-1 was immunohistochemically expressed by tumor cells at a variable level in 39 cases tested. The adjacent normal mucosa was negative for ET-1 expression. Strong ET(A) R expression observed in the deeper infiltrating areas at the periphery of neoplastic tissue correlated significantly with tumor stage. ET(B) R levels were very low or undetectable. Western blot analysis in paired (normal, tumor) fresh-frozen samples of colorectal cancers and in four colon carcinoma cell lines confirmed these findings. In addition, lower levels of ET-1 in the peripheral circulation after the tumor resection were found by ELISA as compared to those observed before surgery.


CONCLUSIONS
ET-1 and ET(A) R, but not ET(B) R, are expressed at a higher level in primary and cultured colon carcinoma cells as compared to normal colon mucosa cells. Further functional studies are needed to explore the role of ET-1/ET(A) R axis in colon carcinogenesis.
Department of Surgery, University of Thessaly, Larissa, Greece.
Paraskevi
P
Liakou
Kostantinos
K
Tepetes
Anastasios
A
Germenis
Vasiliki
V
Leventaki
Vassilis
V
Atsaves
Efstratios
E
Patsouris
Nikolaos
N
Roidis
Konstantinos
K
Hatzitheophilou
George Z
GZ
Rassidakis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000737:chemistry*; D019332:Endothelin-1 / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D044022:Receptor, Endothelin A / Q000032:analysis*; D044023:Receptor, Endothelin B / Q000032:analysis*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B