ArticleThe Journal of experimental medicine2021
Tumor-derived IL-6 and trans-signaling among tumor, fat, and muscle mediate pancreatic cancer cachexia.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.
- Biomarkers of Skeletal Muscle Atrophy Based on Atrogenes Evaluation: A Systematic Review and Meta-Analysis Study.International journal of molecular sciences · 2025Pooled it
- Lipid metabolism associated with efficacy of metronomic capecitabine and camrelizumab in gastrointestinal cancer: an exploratory clinical trial.BMC medicine · 2025Trial
- Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.Cancer discovery · 2026Article
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- Reframing cancer cachexia: from malnutrition to treatable disease.Nature reviews. Endocrinology · 2026Article
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- Otopetrin 1 protects against adipose tissue wasting during cancer cachexia progression.iScience · 2026Article
- Understanding cachexia and muscle dysfunction in the context of metastatic breast cancer.Cancer metastasis reviews · 2026Review
- Chemotherapy induces tissue NADbioRxiv : the preprint server for biology · 2026Article
- Efficacy and safety of tocilizumab for neoplastic fever in patients with advanced solid tumors: a multicenter retrospective study.The oncologist · 2026Article
- Dietary supplementation with ursolic acid preserves skeletal muscle mass and strength in mouse models of cancer cachexia.American journal of physiology. Cell physiology · 2026Article
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Subcutaneous adipose tissue outperforms muscle strength as an indicator of survival and quality of life in patients with cancer: a multicenter cohort study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Observational
- Tumor-muscle communication in cancer-associated cachexia (Review).Oncology letters · 2026Review
- Myosteatosis Predicts Poor Prognosis in Patients With Castration-Resistant Prostate Cancer Treated With Enzalutamide.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- The Eubacterium Rectale Derived Extracellular Vesicles Alleviate Cancer Cachexia Induced Lipolysis by Inhibiting Macrophage Polarization.Journal of extracellular vesicles · 2026Article
- Sarcopenia as a Marker of Immunometabolic Vulnerability in Pancreatic Ductal Adenocarcinoma.Cancers · 2026Review
- Dual Roles of Adipose Tissue in Skeletal Muscle Regeneration: Pro-Regenerative Versus Maladaptive.Journal of cachexia, sarcopenia and muscle · 2026Review
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Most patients with pancreatic adenocarcinoma (PDAC) suffer cachexia; some do not. To model heterogeneity, we used patient-derived orthotopic xenografts. These phenocopied donor weight loss. Furthermore, muscle wasting correlated with mortality and murine IL-6, and human IL-6 associated with the greatest murine cachexia. In cell culture and mice, PDAC cells elicited adipocyte IL-6 expression and IL-6 plus IL-6 receptor (IL6R) in myocytes and blood. PDAC induced adipocyte lipolysis and muscle steatosis, dysmetabolism, and wasting. Depletion of IL-6 from malignant cells halved adipose wasting and abolished myosteatosis, dysmetabolism, and atrophy. In culture, adipocyte lipolysis required soluble (s)IL6R, while IL-6, sIL6R, or palmitate induced myotube atrophy. PDAC cells activated adipocytes to induce myotube wasting and activated myotubes to induce adipocyte lipolysis. Thus, PDAC cachexia results from tissue crosstalk via a feed-forward, IL-6 trans-signaling loop. Malignant cells signal via IL-6 to muscle and fat, muscle to fat via sIL6R, and fat to muscle via lipids and IL-6, all targetable mechanisms for treatment of cachexia.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.