Matrixmetalloproteinases: up-regulated in subclones that survived 10-Gy irradiation.
Matrixmetalloproteinases: up-regulated in subclones that survived 10-Gy irradiation.
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DOI：
10.1007/s11604-007-0168-9
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发表时间：
2007-10-01
影响因子：
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通讯作者：
Shirato, Hiroki
中科院分区：
文献类型：
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作者：
Nishioka, Takeshi;Yasuda, Motoaki;Shirato, Hiroki
我们报告了一项关于 10 Gy 辐射后存活的细胞系 mRNA 表达模式的有趣发现。根据教科书上的线性二次模型，存活曲线在高剂量区域呈直线，这意味着细胞以恒定的速率被杀死。该模型解释了有两种类型的杀伤：α-杀伤，它是剂量 D 的函数，β 杀伤，它是 D 2 的函数。这是击中模型的一种修改版本，其中一定百分比的细胞在辐射后保持完整。我们使用小鼠纤维肉瘤细胞（QRsP，p53野生型）； 1×10 4 个细胞暴露于10Gy。第 12 天，我们收获了约 30 个菌落中的 6 个，并将它们建立为 QRsPIR-1 至 QUsPIR-6。对亲本 QRsP 和 QRsPIR-1 进行 cDNA 微阵列分析。两者之间的模式显着不同，表明存活的细胞并不完整。相反，它们比亲本 QRsP 具有更强的攻击性：基质金属蛋白酶 (MMP) 13（胶原酶）和 MMP3 显着上调（分别为 26 倍和 23 倍）。这些结果鼓励我们进行一项体内研究，其中将 2× 10 4 个细胞皮下注射到 C57BL/6 小鼠（每只 5 只）的胁腹中。第28天，在五只小鼠的每只体内触诊到一个大的肿瘤块，以检测QRSPIR-1。相比之下，只有两只小鼠出现了亲本 QRsP 的肿瘤块。为了形成肿瘤块，必须降解周围组织（主要是胶原蛋白）。我们的发现在这方面很有启发性。
We report an interesting fi nding regarding the mRNA expression pattern of cell lines that survived 10-Gy irradiation. According to the linear quadratic model in a textbook, the survival curve shows a straight line at highdose areas, meaning that cells are killed at a constant rate. The model explains that there are two types of killing: α-killing, which is a function of dose D, and βkilling, which is a function of D 2. This is a kind of modifi ed version of a hit model wherein some percentage of cells remain intact after irradiation. We used mouse fi brosarcoma cells (QRsP, p53 wild type); 1× 10 4 cells were exposed to 10 Gy. At day 12, we harvested 6 of about 30 colonies and established them as QRsPIR-1 to QUsPIR-6. cDNA microarray analysis was performed for the parental QRsP and QRsPIR-1. The pattern was signifi cantly different between the two, suggesting that the cells that survived were not intact. Rather, they had a more aggressive nature than the parental QRsP: matrix metalloproteinase (MMP) 13 (collagenase) and MMP3 were signifi cantly up-regulated (26-fold and 23-fold, respectively). These results encouraged us to perform an in vivo study in which 2× 10 4 cells were injected subcutaneously into the fl anks of C57BL/6 mice (fi ve animals each). At day 28, a large tumor mass was palpated in each of the fi ve mice for QRSPIR-1. In contrast, only two mice developed a tumor mass of the parental QRsP. To form a tumor mass, degradation of surrounding tissue (mainly collagen) must be done. Our fi ndings are quite revealing in this regard.