Host-produced ADAMTS4 Inhibits Early-Stage Tumor Growth
Host-produced ADAMTS4 Inhibits Early-Stage Tumor Growth
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DOI：
10.18926/amo/56071
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发表时间：
2018-06-01
影响因子：
0.5
通讯作者：
Hirohata, Satoshi
中科院分区：
文献类型：
--
作者：
Asano, Keiichi;Edamatsu, Midori;Hirohata, Satoshi
几个研究小组证明，“具有 1 型血小板反应蛋白基序的解整合素样金属蛋白酶 (ADAMTS)”家族蛋白酶在癌症进展中发挥作用。然而，这些蛋白酶的起源和贡献尚不清楚。在这里，我们证明了宿主产生的 ADAMTS4 与早期肿瘤生长之间的关联。小鼠 Lewis 肺癌 (LLC) 肿瘤显示出 Adamts4 和 Adamts5 的显着表达。我们使用 Adamts4(LacZ/LacZ ) 和 Adamts5(LacZ/LacZ) 敲除小鼠检查了宿主来源的 Adamts4 和 Adamts5 对肿瘤生长的贡献和分布。有趣的是，与野生型小鼠相比，Adamts4(LacZ/LacZ) a 小鼠在接种后5、10和12天时表现出增强的肿瘤生长，而Adamts5(LacZ/LacZ)小鼠在肿瘤生长方面没有表现出显着差异。接下来，我们通过 β-半乳糖苷酶 (β-gal) 染色检查了 LLC 荷瘤 Adamts4(LacZ/LacZ ) 小鼠中 LacZ 的分布。我们发现，在接种后 10 天，β-gal 阳性信号严格位于肿瘤的内部区域。多重染色表明，大多数 n-gal 阳性细胞位于 Adamts4(LacZ/LacZ ) 小鼠的肿瘤脉管系统中。有趣的是，接种后 10 天后，β-gal 阳性信号不与双糖链蛋白聚糖共定位，不包括宿主来源的 ADAMTS4 对双糖链蛋白聚糖的裂解。总而言之，这些发现表明，宿主来源的 ADAMTS4 在肿瘤血管中表达，并与早期肿瘤生长相关。
Several research groups demonstrated that 'a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS)'-family proteases play roles in cancer progression. However, the origins and contributions of these proteases are not known. Here, we demonstrate an association between host-produced ADAMTS4 and early-stage tumor growth. Murine Lewis lung carcinoma (LLC) tumors showed marked expressions of Adamts4 and Adamts5. We examined the contributions and distributions of host-derived Adamts4 and Adamts5 on tumor growth, using Adamts4(LacZ/LacZ )and Adamts5(LacZ/LacZ) knockout mice. Interestingly, the Adamts4(LacZ/LacZ) a mice showed enhanced tumor growth compared to wild-type mice at 5-, 10- and 12-days post-inoculation, whereas the Adamts5(LacZ/LacZ ) mice did not show significant differences in tumor growth. We next examined LacZ distribution in LLC tumor-bearing Adamts4(LacZ/LacZ ) mice by (beta-galactosidase (beta-gal) staining. We found that the (beta-gal-positive signals were strictly localized at the interior areas of the tumor at 10 days post-inoculation. Multiple staining demonstrated that most of the n-gal-positive cells were localized at the tumor vasculature in Adamts4(LacZ/LacZ ) mice. Interestingly, (beta-gal-positive signals were not co-localized with biglycan after 10 days post-inoculation, excluding the biglycan cleavage by host-derived ADAMTS4. Taken together, these findings illustrate that host-derived ADAMTS4 was expressed at the tumor vessels and was associated with early-stage tumor growth.