The inflammatory network: bridging senescent stroma and epithelial tumorigenesis.
Cellular senescence or aging, defined by permanent cell cycle arrest, is well known for its evolutionary advantage in protecting the organism from developing cancer; however, it is also acknowledged that aged stromal cells can significantly expedite epithelial tumorigenesis, although exactly how they function to augment tumor formation remains elusive. Recent evidence suggests that this tumor-promoting effect is likely mediated by diffusible pro-inflammatory molecules synthesized and released by senescent stromal fibroblasts, acting in a paracrine fashion on adjacent tumor epithelium. Mobilization of the inflammatory network by senescent fibroblasts has bifurcated roles on the epithelial and stromal compartments, converging on the promotion of epithelial tumorigenesis. A thorough understanding of the regulatory mechanisms underlying these events may lead to improved approaches in cancer treatment.
Shan
Weiwei
W
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Yang
Gong
G
Liu
Jinsong
J
D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology*