Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas.
OBJECTIVE
The effects of leukotriene (LT) D(4) 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 E(2). We investigated possible correlations between distribution of the recently described LTD(4) receptor CysLT(1)R and factors previously shown to be up-regulated by LTD(4) 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
CysLT(1)R was significantly correlated to COX-2, 5-lipoxygenase, and Bcl-x(L). Male subjects more often exhibited high levels of this receptor relative to female subjects, and Dukes' B patients with elevated CysLT(1)R expression showed markedly poorer survival than those with low-level expression. Furthermore, this was paralleled by an increased viability of CysLT(1)R-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/CysLT(1)R signaling facilitates survival of colon cancer cells, which may affect disease outcome. Like COX-2, LTs are accessible targets for pharmacologic treatment.
Ohd
John F
JF
Division of Experimental Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden.
Nielsen
Christian Kamp
CK
Campbell
Joan
J
Landberg
Göran
G
Löfberg
Helge
H
Sjölander
Anita
A
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002470:Cell Survival / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D018077:Receptors, Leukotriene / Q000378:metabolism*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C412375:cysteinyl leukotriene receptor 2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C083169:leukotriene D4 receptor