Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

Autor: Nelson Inácio Pinto, Raquel Galvão Figuerêdo, Fernanda Janku Cabral, Marilia Seelaender, Alessandro Laviano, Paulo S. M. Alcantara, Flavio Tokeshi, Joanna Darck Carola Correia Lima, Aloisio Felipe-Silva, Estefania Simoes, Telma Maria Tenório Zorn, Mychel R. P. T. Morais, Gabriela Salim de Castro, Emidio Marques de Matos-Neto, Michele Joana Alves, José Pinhata Otoch, Emer S. Ferro
Rok vydání: 2019
Předmět:
0301 basic medicine
lcsh:Diseases of the musculoskeletal system
Colorectal cancer
Angiogenesis
neoplasms
0302 clinical medicine
Tumour micro‐environment
Fibrosis
Epidermal growth factor
cachexia
epithelial–mesenchymal components
fibrosis
tumour micro-environment
aged
biomarkers
biopsy
body composition
body mass Index
cells cultured
cytokines
female
fibroblasts
gene expression
humans
hypoxia
immunohistochemistry
male
middle aged
oxidative stress
transforming growth factor beta
tumor microenvironment
signal transduction
Orthopedics and Sports Medicine
Cells
Cultured
lcsh:Human anatomy
030220 oncology & carcinogenesis
Original Article
lcsh:QM1-695
Cachexia
Proinflammatory cytokine
03 medical and health sciences
Physiology (medical)
medicine
business.industry
Cancer
Original Articles
medicine.disease
030104 developmental biology
Cancer research
lcsh:RC925-935
business
Transforming growth factor
Zdroj: Journal of Cachexia, Sarcopenia and Muscle
Journal of Cachexia, Sarcopenia and Muscle, Vol 10, Iss 5, Pp 1045-1059 (2019)
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12441
Popis: 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
Databáze: OpenAIRE
Externí odkaz: