Lafkas Daniel, Trimis George, Papavassiliou Athanasios G, Kiaris Hippokratis
Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece.
Int J Cancer. 2008 Aug 15;123(4):967-71. doi: 10.1002/ijc.23546.
The efficacy of chemotherapy is usually viewed as the outcome of cancer-cell-autonomous processes while the contribution of stroma is being overseen. Here we show that p53 mutations in stromal fibroblasts, a genetic lesion that is detectable in primary breast, prostate and probably other cancers, while they accelerate tumorigenesis they also sensitize tumours against conventional chemotherapy by doxorubicin and cis-platinum. The mechanism by which p53 of stromal fibroblasts affects the response of a tumour against chemotherapy is likely to involve the induction of senescence in the fibroblasts which in turns results in the production of growth factors acting onto the cancer cells by paracrine mechanisms. Our findings identify stromal fibroblasts as important modulators of the efficacy of anticancer therapy.
化疗的疗效通常被视为癌细胞自主过程的结果，而基质的作用则被忽视。我们发现，基质成纤维细胞中的p53突变是一种在原发性乳腺癌、前列腺癌以及可能在其他癌症中都能检测到的基因损伤，这种损伤虽然会加速肿瘤发生，但也会使肿瘤对阿霉素和顺铂等传统化疗药物敏感。基质成纤维细胞中的p53影响肿瘤对化疗反应的机制可能涉及诱导成纤维细胞衰老，进而通过旁分泌机制导致作用于癌细胞的生长因子产生。我们的研究结果表明，基质成纤维细胞是抗癌治疗疗效的重要调节因子。
