Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner
- PMID: 20138012
- DOI: 10.1016/j.ccr.2009.12.041
Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner
Erratum in
- Cancer Cell. 2010 May 18;17(5):523. Arron, Sarah Tuttleton [added]
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-kappaB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be "educated" by carcinoma cells to express proinflammatory genes.
2010 Elsevier Inc. All rights reserved.
Comment in
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La mala educación of tumor-associated macrophages: Diverse pathways and new players.Cancer Cell. 2010 Feb 17;17(2):111-2. doi: 10.1016/j.ccr.2010.01.019. Cancer Cell. 2010. PMID: 20159603
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