Prostaglandin E and prostacyclin receptor expression in tumor and host tissues from MCG 101-bearing mice: a model with prostanoid-related cachexia

• 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.

Nyckelord

Animals

Base Sequence

Body Weight

Cachexia/*physiopathology

DNA Primers

DNA

Complementary/genetics

Dinoprostone/*metabolism

Disease Models

Animal

Energy Intake

Female

Indomethacin/pharmacology

Methylcholanthrene

Mice

Mice

Inbred C57BL

Organ Specificity

Prostaglandins/*physiology

RNA

Messenger/genetics/isolation & purification

RNA

Neoplasm/genetics/isolation & purification

Receptors

Prostaglandin E/drug effects/*genetics

Sarcoma

Experimental/chemically induced/*genetics/physiopathology

Transcription

Genetic

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)