Fibroblasts in the aged pancreas drive pancreatic cancer progression.
Daniel J ZabranskyYash ChhabraMitchell E FaneEmma KartaliaJames M LeathermanLaura HüserJacquelyn W ZimmermanDaniel DelittoSong HanTodd D ArmstrongSamantha GuinnSneha PramodElizabeth D ThompsonSteven J HughesJennifer F O'ConnellJosephine M EganElizabeth D ThompsonAshani T WeeraratnaPublished in: Cancer research (2024)
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 non-malignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Since 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, while 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.
Keyphrases
- extracellular matrix
- middle aged
- signaling pathway
- papillary thyroid
- stem cells
- cell proliferation
- squamous cell carcinoma
- mass spectrometry
- induced apoptosis
- squamous cell
- metabolic syndrome
- physical activity
- single cell
- electronic health record
- intellectual disability
- skeletal muscle
- risk assessment
- atomic force microscopy
- adipose tissue
- artificial intelligence
- human health
- high resolution
- big data