Open AccessMetabolic reprogramming of tumor-associated macrophages by collagen turnover promotes fibrosis in pancreatic cancer
Author(s) -
Madeleine M. LaRue,
Seth J. Parker,
Joseph Puccini,
Michael Cammer,
Alec C. Kimmelman,
Dafna Bar–Sagi
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119168119
Subject(s) - extracellular matrix , tumor microenvironment , microbiology and biotechnology , pancreatic cancer , stroma , immune system , chemistry , hepatic stellate cell , tumor progression , internalization , biology , cancer research , cell , biochemistry , endocrinology , cancer , immunology , genetics , immunohistochemistry , gene
Significance The highly desmoplastic and immunosuppressive microenvironment of pancreatic tumors is a major determinant of the aggressive nature and therapeutic resistance of pancreatic cancer. Therefore, improving our understanding of the mechanisms that regulate the composition and function of the pancreatic tumor microenvironment is critical for the design of intervention strategies for this devastating malignancy. This study identifies a modality for the reprogramming of tumor-associated macrophages involving collagen scavenging followed by a metabolic switch toward a profibrotic paracrine phenotype. These findings establish a molecular framework for the elucidation of regulatory processes that could be harnessed to mitigate the stroma-dependent protumorigenic effects in pancreatic cancer.