Kenny Paraic A, Bissell Mina J
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Int J Cancer. 2003 Dec 10;107(5):688-95. doi: 10.1002/ijc.11491.
Cancer is characterized by unrestrained proliferation and loss of organization, a process that is intimately linked to, and controlled by, reciprocal signaling between the genetically altered tumor epithelium, the stroma, the components of the basement membrane and inflammatory mediators. Much work has been done to characterize the genetics of cancer cells. In this review, we describe the experiments that have been performed, which point to the significant role of the tissue microenvironment in the developmental regulation of normal and neoplastic cells. Using a variety of model systems, the works of a number of laboratories have converged on a hypothesis where the correction of 1 or 2 signaling defects can revert tumor cells to a normal phenotype, both in vivo and in culture, even when the tumor cells possess multiple genetic and epigenetic lesions. This paradigm has been successfully used to treat acute promyelocytic leukemia, and it remains the task of biomedical researchers to identify additional targets for the reversion of other human malignancies.
癌症的特征是不受控制的增殖和组织结构的丧失，这一过程与基因改变的肿瘤上皮、基质、基底膜成分和炎症介质之间的相互信号传导密切相关，并受其控制。为了表征癌细胞的遗传学，已经开展了大量工作。在本综述中，我们描述了所进行的实验，这些实验表明组织微环境在正常细胞和肿瘤细胞的发育调控中具有重要作用。利用各种模型系统，许多实验室的研究都集中在一个假说上，即即使肿瘤细胞存在多种遗传和表观遗传损伤，纠正1或2个信号缺陷也能在体内和体外使肿瘤细胞恢复正常表型。这一范例已成功用于治疗急性早幼粒细胞白血病，生物医学研究人员的任务仍然是确定使其他人类恶性肿瘤逆转的额外靶点。
