title: MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.
abstract: The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Burgos
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Iresjö
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Smedh
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology* / Q000235:genetics; D002100:Cachexia / Q000209:etiology* / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D002149:Energy Intake; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000150:complications* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000097:blood / Q000235:genetics*; D000080866:Nucleobindins; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D014407:Tumor Cells, Cultured; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D013972:Thyrotropin