Heparan sulfate proteoglycans mediate renal carcinoma metastasis.
Heparan sulfate proteoglycans mediate renal carcinoma metastasis.
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DOI：
10.1002/ijc.30397
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发表时间：
2016-12-15
影响因子：
6.4
通讯作者：
Tarbell JM
中科院分区：
文献类型：
--
作者：
Qazi H;Shi ZD;Song JW;Cancel LM;Huang P;Zeng Y;Roberge S;Munn LL;Tarbell JM
肿瘤细胞表面的蛋白聚糖/糖蛋白层（糖萼）与细胞功能相关，可能导致侵袭和转移。此外，具有高转移潜能的侵袭性肿瘤细胞在体外响应于间质流刺激具有增强的侵袭率。我们以前的研究表明，硫酸乙酰肝素（HS）在糖萼中起着重要的作用，在这种流量介导的机械转导和上调的侵袭和转移的潜力。在这项研究中，高转移性肾细胞癌细胞的基因改造，以抑制HS生产敲低其合成酶NDST 1。使用改进的Boyden室和微流控分析，我们表明，流动增强的入侵抑制HS缺陷细胞。为了评估这些细胞在体内转移的能力，将表达荧光报告基因的亲本或敲低细胞注射到SCID小鼠的肾包膜中。组织学分析证实，与具有完整HS的对照细胞相比，由NDST 1敲低细胞形成的肿瘤向远处器官的转移大幅减少（95%）。这些细胞侵入周围组织的能力也受到损害。HS减少后转移和侵袭的实质性抑制表明肿瘤细胞糖萼在肿瘤进展中的积极作用。
The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive tumor cells with high metastatic potential have enhanced invasion rates in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) in the glycocalyx plays an important role in this flow mediated mechanostransduction and upregulation of invasive and metastatic potential. In this study, highly metastatic renal cell carcinoma cells were genetically modified to suppress HS production by knocking down its synthetic enzyme NDST1. Using modified Boyden chamber and microfluidic assays, we show that flow-enhanced invasion is suppressed in HS deficient cells. To assess the ability of these cells to metastasize in vivo, parental or knockdown cells expressing fluorescence reporters were injected into kidney capsules in SCID mice. Histological analysis confirmed that there was a large reduction (95%) in metastasis to distant organs by tumors formed from the NDST1 knockdown cells compared to control cells with intact HS. The ability of these cells to invade surrounding tissue was also impaired. The substantial inhibition of metastasis and invasion upon reduction of HS suggests an active role for the tumor cell glycocalyx in tumor progression.
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通过激活基质金属蛋白酶7，剪切应力促进软骨肉瘤细胞运动、侵袭和肺部定植
影响因子：
--
作者：
Guan PP;Yu X;Guo JJ;Wang Y;Wang T;Li JY;Konstantopoulos K;Wang ZY;Wang P
通讯作者：
Wang P
DOI：
10.1039/c3ib40199e
发表时间：
2014-03
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Ebong EE;Lopez-Quintero SV;Rizzo V;Spray DC;Tarbell JM
通讯作者：
Tarbell JM
影响因子：
24.5
作者：
Jacobetz MA;Chan DS;Neesse A;Bapiro TE;Cook N;Frese KK;Feig C;Nakagawa T;Caldwell ME;Zecchini HI;Lolkema MP;Jiang P;Kultti A;Thompson CB;Maneval DC;Jodrell DI;Frost GI;Shepard HM;Skepper JN;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
4.7
作者：
Hammond E;Khurana A;Shridhar V;Dredge K
通讯作者：
Dredge K
影响因子：
12.4
作者：
Draz MS;Fang BA;Zhang P;Hu Z;Gu S;Weng KC;Gray JW;Chen FF
通讯作者：
Chen FF