학술논문
Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia
Document Type
article
Author
Joanna D.C.C. Lima; Estefania Simoes; Gabriela deCastro; Mychel Raony P.T. Morais; Emidio M. deMatos‐Neto; Michele J. Alves; Nelson I. Pinto; Raquel G. Figueredo; Telma M.T. Zorn; Aloísio S. Felipe‐Silva; Flavio Tokeshi; José P. Otoch; Paulo Alcantara; Fernanda J. Cabral; Emer S. Ferro; Alessandro Laviano; Marilia Seelaender
Source
Journal of Cachexia, Sarcopenia and Muscle, Vol 10, Iss 5, Pp 1045-1059 (2019)
Subject
Language
English
ISSN
2190-6009
2190-5991
2190-5991
Abstract
Abstract Background Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro‐environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro‐environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. Methods 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. Results Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte–macrophage colony‐stimulating factor, interferon‐α, and interleukin (IL)‐8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight‐stable counterparts. Also, IL‐8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α‐smooth muscle actin (P