Dataset: Transcription profiling of mouse cancer associated fibroblasts (CAFs) reveals are activation in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-I?B-dependent manner.
Full title: Cancer Associated Fibroblasts are activated in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-κB-...
Full title: Cancer Associated Fibroblasts are activated in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-κB-dependent manner. 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 cancer, we found a pro-inflammatory gene signature in CAFs isolated from dysplastic skin. This signature was also evident in CAFs from skin as well as mammary and pancreatic tumors in mice, and in human cancer. Surprisingly, the inflammatory signature was already activated in CAFs isolated from the incipient hyperplastic stage in multistep tumorigenesis. CAFs from this pathway functioned to promote macrophage recruitment, neovascularization and tumor growth in vivo, activities abolished when NF-κB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be “educated” by carcinoma cells to express pro-inflammatory genes. Experiment Overall Design: We performed expression profiling analysis of dermal fibroblasts sorted from dysplastic skin tissue of K14-HPV16 mice, and from age matched non transgenic controls. This array analysis was repeated in triplicate. Amplified RNA was hybridized to the 430 2.0 Affymetrix mouse genome arrays.
- Dec.12, 2014
- Nov.11, 2014