Preclinical and clinical studies in our laboratory have suggested that
prostaglandin (PG) E2 is involved in
anorexia and
cachexia development, although the role of COX pathways on the pathogenesis of
cancer cachexia remains to be clarified. Expressions of
PGE (EP1, EP2, EP3alpha,beta,gamma and EP4) and PGI (IP) receptors in the central nervous system (brain cortex, hypothalamus and brain stem), in peripheral (liver, white adipose tissue and skeletal muscle) and
tumor tissue from MCG-101-bearing mice with and without
indomethacin treatment were investigated by RT-PCR and immunohistochemistry. Expression of EP1 in the liver and EP4 receptor in white adipose tissue were upregulated and responded to
indomethacin treatment, while downregulated expression of EP3 in skeletal muscle from
tumor-bearing mice was unresponsive to
indomethacin treatment despite improved carcass weight. Expression of EP and IP receptors in brain and
tumor tissue from
tumor-bearing mice were neither related nor responsive to systemic
PGE2 levels including increased IL-1beta,
IL-6 and
TNF-alpha host activities. The expression IP receptor in CNS, peripheral tissue and
tumor tissue was unchanged by
cachexia development. Our results suggest that transcription of EP receptors in liver, fat and skeletal muscle tissue may be a control level for host metabolic alterations during
tumor progression, while overall EP and IP receptor expression in CNS did not indicate an important control level for appetite regulation in MCG 101-bearing mice despite
prostanoid related
anorexia.