Anorexia and cachexia in prostaglandin EP1 and EP3 subtype receptor knockout mice bearing a tumor with high intrinsic PGE2 production and prostaglandin related cachexia.
Previous studies in our laboratory have suggested that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. However, the role of COX pathways in the pathogenesis of cancer anorexia/cachexia is not fully resolved. In the present study, we investigated the role of PGE receptors subtype EP1 and EP3 on the development of anorexia in MCG 101-bearing mice. Our results show that the absence of host EP1 or EP3 receptors did not alter the magnitude of anorexia in tumor-bearers. However, anorexia in tumor-bearing EP1 and EP3 knockouts was not improved by indomethacin treatment as observed in wild type tumor-bearers. By contrast, indomethacin improved body composition similar in EP1 and EP3 knockouts as well as in wild type tumor-bearing animals and tumor growth was retarded in EP1 and promoted in EP3 knock outs. Our results demonstrate that host EP1 and EP3 receptors are involved in the control of local tumor growth, which translates into anorexia, this being the main cause of metabolic adaptive alterations to explain weight loss in this model. Brain EP1 and EP3 subtype receptors do not seem to directly control anorexia, which leaves EP2 and EP4 as potential candidates.
Wang
W
W
Dept. of Surgery, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg, Sweden.
Andersson
M
M
Lönnroth
C
C
Svanberg
E
E
Lundholm
K
K
D000821:Animal Feed; D000818:Animals; D000855:Anorexia / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D002100:Cachexia / Q000378:metabolism* / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000097:blood; D005223:Fats / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018078:Receptors, Prostaglandin E / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype
D005223:Fats; D015850:Interleukin-6; C545636:Ptger1 protein, mouse; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015232:Dinoprostone