Lloyd B H, Platt-Higgins A, Rudland P S, Barraclough R
School of Biological Sciences, University of Liverpool, UK.
Oncogene. 1998 Jul 30;17(4):465-73. doi: 10.1038/sj.onc.1201948.
The rodent S100-related calcium-binding protein, S100A4 induces metastasis in non-metastatic rat and mouse benign mammary cells and co-operates with benign-tumour-inducing changes in two transgenic mouse models, to yield metastatic mammary tumours. Co-transfection of the human gene for S100A4 with pSV2neo into the benign rat mammary cell line, Rama 37, yielded cells which expressed a low level of the endogenous S100A4 mRNA, and either high or undetectable levels of human S100A4 mRNA. The cells which expressed a high level of human S100A4 mRNA induced metastasis in the benign rat mammary cell line Rama 37 in an in vivo assay, whereas the cells which expressed an undetectable level of human S100A4 did not induce any detectable metastases. The primary tumours arising from the S100A4-expressing cells contained high levels of immunocytochemically-detected S100A4 and this high level of S100A4 and the metastatic potential were maintained when cells from a metastasis were re-injected into syngeneic rats. The results show that the human S100A4 possesses metastasis-inducing capabilities.
啮齿动物的S100相关钙结合蛋白S100A4可诱导非转移性大鼠和小鼠良性乳腺细胞发生转移，并在两种转基因小鼠模型中与良性肿瘤诱导变化协同作用，产生转移性乳腺肿瘤。将人S100A4基因与pSV2neo共转染到良性大鼠乳腺细胞系Rama 37中，得到的细胞内源性S100A4 mRNA表达水平较低，人S100A4 mRNA表达水平较高或检测不到。在体内试验中，表达高水平人S100A4 mRNA的细胞可诱导良性大鼠乳腺细胞系Rama 37发生转移，而表达水平检测不到的人S100A4的细胞则未诱导任何可检测到的转移。由表达S100A4的细胞产生的原发性肿瘤含有高水平的免疫细胞化学检测到的S100A4，当将转移灶中的细胞重新注射到同基因大鼠体内时，这种高水平的S100A4和转移潜能得以维持。结果表明，人S100A4具有诱导转移的能力。
