@article{7e4242985f924d2cb6ec292176463c2f,
title = "Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-κB-Dependent Manner",
abstract = "Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin carcinogenesis, we found a proinflammatory gene signature in CAFs isolated from dysplastic skin. This signature was maintained in CAFs from subsequent skin carcinomas and was evident in mammary and pancreatic tumors in mice and in cognate human cancers. The inflammatory signature was already activated in CAFs isolated from the initial hyperplastic stage in multistep skin tumorigenesis. CAFs from this pathway promoted macrophage recruitment, neovascularization, and tumor growth, activities that are abolished when NF-κB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be {"}educated{"} by carcinoma cells to express proinflammatory genes.",
keywords = "CELLCYCLE, CELLIMMUNO, SIGNALING",
author = "Neta Erez and Morgan Truitt and Peter Olson and Douglas Hanahan",
note = "Funding Information: We thank Z. Werb, L. Coussens, T. Tlsty, L. Landsman, and J. Erler for comments on the manuscript; O. Nolan-Stevaux for scientific discussions and comments on the manuscript; E. Nakakura and S. Tuttleton Arron for providing us with human PDAC and SCC samples; L. Coussens for providing HPV16/FcRγ −/− mice; T. Rambaldo and P. Dazin for providing FACS sorting services; and M. Tocornal for art work. We thank the Sandler Center Lentiviral Core at UCSF for their expertise and RNAi services rendered, as well as the Diabetes Center's Microscopy Core, the J. David Gladstone Genomics Core Laboratory, and the Genome Analysis Core, Helen Diller Family Comprehensive Cancer Center, UCSF. The research was supported by grants from the National Cancer Institute (to D.H.). N.E. acknowledges a postdoctoral fellowship from the Irving Institute Fellowship Program of the Cancer Research Institute. P.O. acknowledges support from NCI Training Grant T32 CA09043 (Director J. Michael Bishop), Molecular Analysis of Tumor Viruses. D.H. is an American Cancer Society Research Professor. ",
year = "2010",
month = feb,
day = "17",
doi = "10.1016/j.ccr.2009.12.041",
language = "אנגלית",
volume = "17",
pages = "135--147",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}
