Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma.

By A. Rhim, P. Oberstein, Dafydd H. Thomas, Emily T Mirek, Carmine F. Palermo, Stephen A. Sastra, Erin N Dekleva, T. Saunders, Claudia P. Becerra, I. Tattersall and 7 more. Cancer Cell, 2014

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Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich desmoplastic stroma. To better understand its role in malignant progression, we deleted Shh in a well-defined mouse model of PDAC. As predicted, Shh-deficient tumors had reduced stromal content. Surprisingly, such tumors were more aggressive and exhibited undifferentiated histology, increased vascularity, and heightened proliferation--features that were fully recapitulated in control mice treated with a Smoothened inhibitor. Furthermore, administration of VEGFR blocking antibody selectively improved survival of Shh-deficient tumors, indicating that Hedgehog-driven stroma suppresses tumor growth in part by restraining tumor angiogenesis. Together, these data demonstrate that some components of the tumor stroma can act to restrain tumor growth.

Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/1a7a075d29fcb31432b332700f7787d050de9f50

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Citations in the corpus

Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. (2019, background): “Additionally, chronic treatment with a Smoothened inhibitor or neoplastic cell deletion of Sonic Hedgehog 1, a major mediator of desmoplasia, in a PDAC mouse model resulted in a similar phenotype (20, 21).”
New horizons in tumor microenvironment biology: challenges and opportunities (2015, background): “The naive stroma is a critical compartment in maintaining physiological homeostasis of normal tissue, and recent studies strengthened the concept that some stromal components have anticancer activities by regulating immunosuppression and restraining carcinogenesis, which is particularly the case of ”
IL-1-induced JAK/STAT signaling is antagonized by TGF-β to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. (2018, background): “The benefits of targeting iCAFs would be two-fold: depleting iCAFs would reduce the secretion of tumor-promoting cytokines and chemokines, and shifting iCAFs to a more myofibroblastic state would increase the αSMA-positive CAF population that has been previously suggested to restrain tumor progressi”