Barraclough R, Chen H J, Davies B R, Davies M P, Ke Y, Lloyd B H, Oates A, Rudland P S
Department of Biochemistry, University of Liverpool, U.K.
Biochem Soc Symp. 1998;63:273-94.
The metastatic spread of cancer is a little understood process, in part because it is difficult to model the entire process using experimental approaches in vitro. The ability to transfer DNA into non-metastatic mammary cells and to observe the induction of metastasis in vivo provides a means for identifying DNA sequences that are associated with the development of metastatic capability. Using these techniques, a metastasis-associated cytoskeletal calcium binding protein, S100A4 (p9Ka), has been identified as an inducer of metastatic capability in benign rat mammary epithelial cells. Metastasis can also be induced in the rat mammary epithelial cells by fragments of DNA from metastatic, but not from benign, human breast tumour cells. These non-coding fragments of DNA act via the induction of osteopontin, an extracellular, integrin binding, calcium binding protein. Since both osteopontin and S100A4 are thought to be associated with malignancy in human breast cancer specimens, gene transfer techniques can identify genes for metastasis-inducing proteins that may play a role in breast cancer, and further suggest that cell migration/motility might be important in the metastatic process.
癌症的转移扩散是一个鲜为人知的过程，部分原因是很难在体外使用实验方法对整个过程进行建模。将DNA导入非转移性乳腺细胞并在体内观察转移诱导的能力，为鉴定与转移能力发展相关的DNA序列提供了一种手段。利用这些技术，一种与转移相关的细胞骨架钙结合蛋白S100A4（p9Ka）已被鉴定为良性大鼠乳腺上皮细胞转移能力的诱导物。来自转移性而非良性人乳腺肿瘤细胞的DNA片段也可在大鼠乳腺上皮细胞中诱导转移。这些非编码DNA片段通过诱导骨桥蛋白起作用，骨桥蛋白是一种细胞外、整合素结合、钙结合蛋白。由于骨桥蛋白和S100A4都被认为与人类乳腺癌标本中的恶性肿瘤有关，基因转移技术可以识别可能在乳腺癌中起作用的转移诱导蛋白的基因，并进一步表明细胞迁移/运动性在转移过程中可能很重要。
