ArticleCancer research2024
Fibroblasts in the Aged Pancreas Drive Pancreatic Cancer Progression.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting the CAF-GDF15 axis attenuates AKT-mediated mitochondrial rewiring and chemoradiation resistance in esophageal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Cancer-Associated Fibroblasts Promote Epithelial-Mesenchymal Transition and Classical to Basal Subtype Shift in Pancreatic Cancer.Cancer research · 2026Article
- An interpretable machine learning model for predicting survival in pancreatic cancer via SHAP: a multicenter study.Journal of gastroenterology · 2026Article
- Research progress on the biological function and molecular mechanism of GDF-15 in solid malignant tumors.World journal of surgical oncology · 2026Review
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
- Growth differentiation factor-15 (GDF-15) in localized pancreatic adenocarcinoma treated with multiagent chemotherapy: a biomarker analysis from the NEOLAP trial (AIO-PAK-0113).ESMO gastrointestinal oncology · 2026Article
- The Aging Microenvironment Is a Determinant of Immune Exclusion and Metastatic Fate in Pancreatic Cancer.Cancer research · 2026Article
- Pancreatic cancer-associated myofibroblasts: a review.International journal of biological sciences · 2026Review
- Machine-learning CT radiomics for prognostication in unresectable pancreatic cancer.Frontiers in pharmacology · 2026Article
- Mucin 5ac modulates cancer-associated fibroblast heterogeneity through epigenetic reprogramming of precursor cells.American journal of physiology. Cell physiology · 2026Article
- Pancreatic cancer in China: the analysis of cancer mortality and burden in China, 2008-2021.BMC cancer · 2025Article
- Peritumoral colonic epithelial cell-derived GDF15 sustains colorectal cancer via regulation of glycolysis and histone lactylation.Nature aging · 2025Article
- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- Unveiling GDF15 as a promising biomarker for predicting survival in pancreatic ductal carcinoma: a retrospective research.BMC cancer · 2025Article
- Cancer progression through the lens of age-induced metabolic reprogramming.Nature reviews. Cancer · 2025Review
- Stromal senescence contributes to age-related increases in cancer.Nature reviews. Cancer · 2025Review
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Machine learning-guided single-cell multiomics uncovers GDF15-driven immunosuppressive niches in NSCLC: A translational framework for overcoming anti-PD-1 resistance.Translational oncology · 2025Article
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in nonmalignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Because fibroblasts have profound impacts on pancreatic cancer progression, we investigated whether age-related changes in pancreatic fibroblasts influence cancer growth and metastasis. Proteomics analysis revealed that aged fibroblasts secrete different factors than young fibroblasts, including increased growth/differentiation factor 15 (GDF-15). Treating young mice with GDF-15 enhanced tumor growth, whereas aged GDF-15 knockout mice showed reduced tumor growth. GDF-15 activated AKT, rendering tumors sensitive to AKT inhibition in an aged but not young microenvironment. These data provide evidence for how aging alters pancreatic fibroblasts and promotes tumor progression, providing potential therapeutic targets and avenues for studying pancreatic cancer while accounting for the effects of aging. SIGNIFICANCE: Aged pancreatic fibroblasts secrete GDF-15 and activate AKT signaling to promote pancreatic cancer growth, highlighting the critical role of aging-mediated changes in the pancreatic cancer microenvironment in driving tumor progression. See related commentary by Isaacson et al., p. 1185.
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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.