Shan Weiwei, Yang Gong, Liu Jinsong
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Front Biosci (Landmark Ed). 2009 Jan 1;14(11):4044-57. doi: 10.2741/3511.
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.
细胞衰老，即由永久性细胞周期停滞所定义的现象，因其在保护机体免受癌症侵袭方面的进化优势而广为人知；然而，人们也认识到，衰老的基质细胞能够显著加速上皮肿瘤的发生，尽管它们究竟如何促进肿瘤形成仍不清楚。最近的证据表明，这种促肿瘤效应可能是由衰老的基质成纤维细胞合成并释放的可扩散促炎分子介导的，这些分子以旁分泌方式作用于相邻的肿瘤上皮。衰老的成纤维细胞对炎症网络的调动在上皮和基质区室中具有双重作用，最终促进上皮肿瘤的发生。深入了解这些事件背后的调控机制可能会带来改进的癌症治疗方法。
