Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines.
Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines.
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DOI：
10.1016/j.bbrc.2015.12.074
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发表时间：
2016-01
影响因子：
3.1
通讯作者：
N. Tsunekawa;Nobuaki Higashi;Yusuke Kogane;M. Waki;Hiroaki Shida;Y. Nishimura;H. Adachi;M. Nakajima-M.
中科院分区：
文献类型：
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作者：
N. Tsunekawa;Nobuaki Higashi;Yusuke Kogane;M. Waki;Hiroaki Shida;Y. Nishimura;H. Adachi;M. Nakajima-M.
为了探索肝素酶在癌症-宿主串扰中的可能作用，我们研究了肝素酶是否影响结直肠癌细胞中炎症趋化因子的表达。用肝素酶孵育的小鼠结直肠癌细胞上调MCP-1、KC和RANTES基因，释放MCP-1和KC蛋白。在两种人类结直肠癌细胞系中检测到肝素酶依赖性IL-8的产生。添加肝素酶抑制剂Heparastatin （SF4）不影响MCP-1的产生，而潜在和成熟形式的肝素酶都增加了MCP-1的释放，这表明肝素酶的催化活性对于MCP-1的产生是必不可少的。相反，在培养基中加入肝素以剂量依赖的方式抑制MCP-1的释放。同样，通过RNAi靶向抑制Ext1可显著抑制结肠26细胞中硫酸肝素的细胞表面表达和MCP-1的产生。综上所述，结肠26细胞通过硫酸肝素结合转导肝素酶介导的信号。我们提出了一种独立于其内糖苷酶活性的肝素酶的新功能，即作为趋化因子产生的兴奋剂。
To explore possible roles of heparanase in cancer-host crosstalk, we examined whether heparanase influences expression of inflammatory chemokines in colorectal cancer cells. Murine colorectal carcinoma cells incubated with heparanase upregulated MCP-1, KC, and RANTES genes and released MCP-1 and KC proteins. Heparanase-dependent production of IL-8 was detected in two human colorectal carcinoma cell lines. Addition of a heparanase inhibitor Heparastatin (SF4) did not influence MCP-1 production, while both latent and mature forms of heparanase augmented MCP-1 release, suggesting that heparanase catalytic activity was dispensable for MCP-1 production. In contrast, addition of heparin to the medium suppressed MCP-1 release in a dose-dependent manner. Similarly, targeted suppression of Ext1 by RNAi significantly suppressed cell surface expression of heparan sulfate and MCP-1 production in colon 26 cells. Taken together, it is concluded that colon 26 cells transduce the heparanase-mediated signal through heparan sulfate binding. We propose a novel function for heparanase independent of its endoglycosidase activity, namely as a stimulant for chemokine production.