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.
Subject(s)
Cancer-Associated Fibroblasts , Pancreatic Neoplasms , Animals , Mice , Growth Differentiation Factor 15/genetics , Growth Differentiation Factor 15/therapeutic use , Proto-Oncogene Proteins c-akt , Pancreatic Neoplasms/pathology , Pancreas/pathology , Fibroblasts/pathology , Tumor Microenvironment , Cell Line, Tumor , Cancer-Associated Fibroblasts/pathologyABSTRACT
The draft genome sequence of Bacillus subtilis A1, isolated from beach soil, has been shown to produce biofilm. The genome size is 4,215,114 bp with an average G+C content of 43.5%. The genome of Bacillus subtilis A1 has 4413 total genes which include 4166 protein-coding sequences, 126 pseudo genes, 10 rRNA genes with 3 operons (5S, 16S and 23S), 86 tRNA genes and 5 noncoding RNA (ncRNA) genes. The genome contains genes coding for surfactin, fengycin, bacillaene, sublancin 168, bacillibactin, subtilosin A, bacilysin. The whole genome project has been deposited in GenBank under the accession number CP075344.1. The raw data is available at https://www.ncbi.nlm.nih.gov/nuccore/CP075344.1.
