Fibronectin Matrix Formation is a Prerequisite for Colonization of Kidney Tumor Cells in Fibrin.
Fibronectin Matrix Formation is a Prerequisite for Colonization of Kidney Tumor Cells in Fibrin.
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DOI：
10.7150/jca.10496
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发表时间：
2015
影响因子：
3.9
通讯作者：
Pilch J
中科院分区：
文献类型：
--
作者：
Knowles LM;Gurski LA;Maranchie JK;Pilch J
纤维蛋白在肺转移中起重要作用。在这里，我们展示了纤维蛋白促进来自肾转移患者的原代肾肿瘤细胞的集落形成。此外，我们发现凝血酶抑制剂水飞蓟素在裸鼠体内抑制纤维蛋白的形成显著减少了肾肿瘤细胞的转移生长。与Matrigel相比，包埋在纤维蛋白中的肿瘤细胞的集落形成效率明显更高，这种效果与肿瘤细胞组装纤维连接蛋白基质和产生应力纤维的能力有关。有趣的是，纤维蛋白中的应力纤维形成是转移性肾肿瘤细胞的特有功能，而非转移性肿瘤细胞仍然是圆形的。Rho激酶抑制剂Y-27632抑制应力纤维的形成，进而减少纤维连接蛋白基质的组装和纤维蛋白中克隆的形成，这表明扩散是转移性肾肿瘤细胞生长的关键机制。总体而言，我们的结果表明，与纤维蛋白的黏附相互作用在肾癌的进展中起着重要作用，抑制这些相互作用可能是治疗和预防肾癌转移的一种有前途的策略。
Fibrin plays an important role in lung metastasis. Here we show that fibrin promotes colony formation in primary kidney tumor cells from patients with kidney metastasis. In addition, we found that inhibition of fibrin formation with the thrombin inhibitor hirudin in nude mice in vivo significantly reduced the metastatic outgrowth of kidney tumor cells. Colony formation was significantly more efficient in tumor cells embedded in fibrin compared to matrigel and this effect correlates with the capacity of tumor cells to assemble a fibronectin matrix and generate stress fibers. Interestingly, stress fiber formation in fibrin was a specific function of metastatic kidney tumor cells while non-metastatic cells remained round. Inhibition of stress fiber formation with the Rho kinase inhibitor Y-27632, in turn, reduced fibronectin matrix assembly and colony formation in fibrin suggesting that spreading is a critical mechanism for the outgrowth of metastatic kidney tumor cells. Overall, our results indicate that adhesive interactions with fibrin play an important role for the progression of renal cell carcinoma and that inhibiting these interactions could be a promising strategy for treatment and prevention of kidney cancer metastasis.
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影响因子：
64.5
作者：
Jan, YW;Matter, M;Ruoslahti, E
通讯作者：
Ruoslahti, E
影响因子：
11.2
作者：
Barkan D;Kleinman H;Simmons JL;Asmussen H;Kamaraju AK;Hoenorhoff MJ;Liu ZY;Costes SV;Cho EH;Lockett S;Khanna C;Chambers AF;Green JE
通讯作者：
Green JE
影响因子：
11.2
作者：
Knowles LM;Gurski LA;Engel C;Gnarra JR;Maranchie JK;Pilch J
通讯作者：
Pilch J
影响因子：
50.3
作者：
Maranchie, JK;Vasselli, JR;Klausner, RD
通讯作者：
Klausner, RD
影响因子：
11.2
作者：
Chaffer, Christine L.;Brennan, Janelle P.;Williams, Elizabeth D.
通讯作者：
Williams, Elizabeth D.