NF-kappa Bp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients

Author(s):Show less -

Camargo, Rodolfo Gonzalez ^[1] ; dos Reis Riccardi, Daniela Mendes ^[1] ; Teixeira Ribeiro, Henrique Quintas ^[1] ; Carnevali, Jr., Luiz Carlos ^[1] ; de Matos-Neto, Emidio Marques ^[1] ; Enjiu, Lucas ^[1] ; Neves, Rodrigo Xavier ^[1] ; Carola Correia Lima, Joanna Darck ^[1] ; Figueredo, Raquel Galvao ^[1] ; Martins de Alcantara, Paulo Sergio ^[2] ; Maximiano, Linda ^[2] ; Otoch, Jose ^[2] ; Batista, Jr., Miguel Luiz ^[3] ; Pueschel, Gerhard ^[4] ; Seelaender, Marilia ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Canc Metab Res Grp, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Clin Surg, BR-05508000 Sao Paulo - Brazil

^[3] Univ Mogi das Cruzes, Biotechnol Grp, Lab Adipose Tissue Biol, BR-05508100 Sao Paulo - Brazil

^[4] Univ Potsdam, Dept Nutr Biochem, D-14558 Potsdam - Germany

• Document type: Journal article
• Source: NUTRIENTS; v. 7, n. 6, p. 4465-4479, JUN 2015.
• Web of Science Citations: 11

Abstract

Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-B). We have examined the gene expression of the subunits NF-Bp65 and NF-Bp50, as well as NF-Bp65 and NF-Bp50 binding, the gene expression of pro-inflammatory mediators under NF-B control (IL-1, IL-6, INF-, TNF-, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IB-). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-Bp65 and its target genes expression (TNF-, IL-1, MCP-1 and IB-) were significantly higher in cachectic cancer patients. Moreover, NF-Bp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-B pathway plays a role in the promotion of WAT inflammation during cachexia. (AU)

• FAPESP's process: 12/50079-0 - Systemic inflammation in cachectic cancer patients: mechanisms and therapeutical strategies, a translational medicine approach
• Grantee: Marilia Cerqueira Leite Seelaender
• Support Opportunities: Research Projects - Thematic Grants