Biological properties and gene expression associated with metastatic potential of human osteosarcoma
Biological properties and gene expression associated with metastatic potential of human osteosarcoma
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DOI：
10.1023/a:1027355610603
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Yokota, J
中科院分区：
文献类型：
--
作者：
Nakano, T;Tani, M;Yokota, J
肺转移对骨肉瘤患者的预后有很大影响。我们以前建立了两个高转移的亚系，M112和M132，从HuO 9人骨肉瘤细胞系通过体内选择。在这项研究中，我们新分离出一个高转移的亚系，H3，和三个低转移的亚系，L 6，L12和L13，从HuO 9的稀释平板法。三个高转移性亚系在肺中产生超过200个转移性结节，而三个低转移性亚系在将2 × 10（6）个细胞注射到裸鼠尾静脉后没有或很少产生结节。高转移和低转移亚系的运动性和侵袭性存在显著差异，而体外生长率和体内致瘤性与其转移能力无关。早期粘附培养板显着降低，在两个低转移的亚系，这占据了较小的表面积比其他亚系的培养板。通过cDNA微阵列比较637个肿瘤相关基因的表达，发现7个基因在高转移和低转移亚系之间差异表达。其中，5个基因（AXL、TGFA、COLL 7A 1、WNT 5A和MKK 6）与粘附性、运动性和/或侵袭性相关。这些结果表明，运动/侵袭和粘附能力的差异是骨肉瘤肺转移的关键决定因素。
Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 x 10(6) cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high-and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness and adhesive abilities are key determinants of lung metastasis in osteosarcoma.