Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas

John F. Öhd, Christian Kamp Nielsen, Joan Campbell, Göran Landberg, Helge Löfberg, Anita Sjölander

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background & Aims: The effects of leukotriene (LT) D4 on intestinal epithelial cells govern events that are involved in cell survival and colon cancer, notably increased expression of cyclooxygenase (COX)-2 and enhanced production of prostaglandin E2. We investigated possible correlations between distribution of the recently described LTD4 receptor CysLT1R and factors previously shown to be up-regulated by LTD4 as well as clinicopathologic traits. Methods: Immunohistochemistry and in situ hybridization were performed on tissue arrays, which were made using colorectal cancer samples from 84 patients. Results: CysLT1R was significantly correlated to COX-2, 5-lipoxygenase, and Bcl-xL. Male subjects more often exhibited high levels of this receptor relative to female subjects, and Dukes' B patients with elevated CysLT1R expression showed markedly poorer survival than those with low-level expression. Furthermore, this was paralleled by an increased viability of CysLT1R-overexpressing cells in a colon cancer cell line. Conclusions: Our results further implicate the involvement of LTs in colorectal carcinoma. Based on our present and earlier findings, we propose that LT/CysLT1R signaling facilitates survival of colon cancer cells, which may affect disease outcome. Like COX-2, LTs are accessible targets for pharmacologic treatment.
    Original languageEnglish
    Pages (from-to)57-70
    Number of pages13
    JournalGastroenterology
    Volume124
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2003

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