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Examination of matricellular fibrosis and wound healing in a model of pancreatic cancer progression

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has the highest amount of stroma when compared to other solid tumors. It is now well known that the stroma plays an important role in supporting pancreatic cancer development and progression and this knowledge has led to the development of potential anti-stromal therapies, some of which have shown synergistic effect in combination with gemcitabine. Despite the acknowledgement of its importance, a granular view of how stromal composition and cross-linking change during the course of PDAC progression remains unfounded. Generally, the fibrosis that occurs in solid tumors appears to be driven primarily by increases in the abundance of fibrillar collagen, whose insolubility is determined by the formation of covalent intermolecular cross-links. Here we have used semi-quantitative proteomics and cross-linked amino acid analysis to characterize the composition and crosslinking status of normal pancreatic and PDAC stroma. In order to mimic the desmoplastic stroma observed in human disease, we utilized the genetically engineered KTC mouse model of PDAC (KrasLSL-G12D/+Tgfbr2flox/+Ptf1a-Cre). We found that highly fibrotic PDACs alter the solubility of their collagen-rich stroma through changes in the abundance of collagen cross-links and supports development of matricellular fibrosis associated with a wound healing response.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Kirk Hansen

PROVIDER: MSV000081553 | MassIVE |

SECONDARY ACCESSION(S): PXD007816

REPOSITORIES: MassIVE

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