Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Endocr Relat Cancer. 2012 Oct 30;19(6):R187-204. doi: 10.1530/ERC-12-0085. Print 2012 Dec.
Reactive stroma initiates during early prostate cancer development and coevolves with prostate cancer progression. Previous studies have defined the key markers of reactive stroma and have established that reactive stroma biology influences prostate tumorigenesis and progression. The stem/progenitor cells of origin and the mechanisms that regulate their recruitment and activation to myofibroblasts or carcinoma-associated fibroblasts are essentially unknown. Key regulatory factors have been identified, including transforming growth factor β, interleukin-8, fibroblast growth factors, connective tissue growth factor, wingless homologs-Wnts, and stromal cell-derived factor-1, among others. The biology of reactive stroma in cancer is similar to the more predictable biology of the stroma compartment during wound repair at sites where the epithelial barrier function is breached and a stromal response is generated. The coevolution of reactive stroma and the biology of how reactive stroma-carcinoma interactions regulate cancer progression and metastasis are targets for new therapeutic approaches. Such approaches are strategically designed to inhibit cancer progression by uncoupling the reactive stroma niche.
反应性基质在前列腺癌早期发展过程中启动，并与前列腺癌的进展共同演变。先前的研究已经定义了反应性基质的关键标志物，并确定了反应性基质生物学影响前列腺肿瘤发生和进展。其起源的干细胞/祖细胞以及调节其募集和激活为肌纤维母细胞或癌相关成纤维细胞的机制在本质上是未知的。已经确定了关键的调节因子，包括转化生长因子β、白细胞介素 8、成纤维细胞生长因子、结缔组织生长因子、Wnt 同源物-Wnts 和基质细胞衍生因子 1 等。癌症中反应性基质的生物学与上皮屏障功能被破坏并产生基质反应的部位的创伤修复过程中基质区室更可预测的生物学相似。反应性基质的共同演变以及反应性基质与癌细胞相互作用调节癌症进展和转移的生物学是新治疗方法的目标。这些方法的设计策略是通过分离反应性基质小生境来抑制癌症进展。
