Expression patterns of endothelin-1 and its receptors in colorectal cancer

Abstract

Background and Objectives 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 (ETAR) and ET-B (ETBR) 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 ETAR expression observed in the deeper infiltrating areas at the periphery of neoplastic tissue correlated significantly with tumor stage. ETBR 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 ETAR, but not ETBR, 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/ETAR axis in colon carcinogenesis. J. Surg. Oncol. 2012; 105: 643-649. (C) 2011 Wiley Periodicals, Inc.