ArticleJournal of cachexia, sarcopenia and muscle2019
Tumour-derived transforming growth factor-β signalling contributes to fibrosis in patients with cancer cachexia.
Article in Journal of cachexia, sarcopenia and muscle, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Circulating MicroRNAs Reflect Systemic Inflammation and Metabolic Dysfunction in Oesophageal Squamous Cell Carcinoma-Associated Cachexia.Journal of cachexia, sarcopenia and muscle · 2026Article
- Article
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Cancer-Associated Cachexia in the Era of Obesity.International journal of molecular sciences · 2025Review
- SPP1Scientific reports · 2025Article
- Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development.Molecular cancer · 2025Review
- Targeting cancer-induced skeletal damage: a holistic approach to understanding pathophysiology, mechanisms, and management solutions.American journal of cancer research · 2025Review
- l-Carnitine relieves cachexia-related skeletal muscle fibrosis by inducing deltex E3 ubiquitin ligase 3L to negatively regulate the Runx2/COL1A1 axis.Journal of cachexia, sarcopenia and muscle · 2024Article
- The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health.Current osteoporosis reports · 2024Review
- Immune System Disorder and Cancer-Associated Cachexia.Cancers · 2024Review
- Immunoregulation in cancer-associated cachexia.Journal of advanced research · 2024Review
- Decoding tumor-fibrosis interplay: mechanisms, impact on progression, and innovative therapeutic strategies.Frontiers in pharmacology · 2024Review
- Is MG53 a potential therapeutic target for cancer?Frontiers in endocrinology · 2023Review
- Exosomal IL-8 derived from Lung Cancer and Colon Cancer cells induced adipocyte atrophy via NF-κB signaling pathway.Lipids in health and disease · 2022Article
- Review
- Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation.Nature communications · 2022Article
- Physical Activity as the Best Supportive Care in Cancer: The Clinician's and the Researcher's Perspectives.Cancers · 2022Review
- Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.Cancer metastasis reviews · 2022Review
- Review
- Cancer Cachexia and Antitumor Immunity: Common Mediators and Potential Targets for New Therapies.Life (Basel, Switzerland) · 2022Review
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundCachexia 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.
methods74 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.
resultsHigher 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 < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)-β1, TGF-β2, and TGF-β3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen-activated protein kinase alteration. Hypoxia-inducible factor-1α mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight-stable group (P = 0.005).
conclusionsOur results demonstrate TGF-β pathway activation in the tumour in cachexia, through the (non-canonical) mitogen-activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF-β-induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.
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