SPARC Regulates Transforming Growth Factor Beta Induced (TGFBI) Extracellular Matrix Deposition and Paclitaxel Response in Ovarian Cancer Cells.
SPARC Regulates Transforming Growth Factor Beta Induced (TGFBI) Extracellular Matrix Deposition and Paclitaxel Response in Ovarian Cancer Cells.
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DOI：
10.1371/journal.pone.0162698
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Brenton JD
中科院分区：
文献类型：
--
作者：
Tumbarello DA;Andrews MR;Brenton JD
TGFBI已显示通过调节微管稳定性的整合素受体介导的机制使卵巢癌细胞对紫杉醇的细胞毒性作用敏感。在此，我们确定TGFBI定位于间皮来源的ECM中有组织的纤维状结构内。我们确定，通过shRNA抑制TGF β 1表达减少了TGFBI在间皮来源的ECM中的沉积，而不影响其整体蛋白表达或分泌。相反，过表达的TGF β 1增加TGFBI沉积。由Met 5a细胞系表达的SPARC-YFP融合构建体与TGFBI共定位在细胞衍生的ECM中。有趣的是，在体外产生的TGFBI能够沉淀从细胞裂解物依赖于一个完整的TGFBI的羧基末端与体外结合试验验证直接相互作用。已显示TGFB 1的最后37个氨基酸是TGFBI相互作用所需的，而缺乏该区域（aa 1-256）的SPARC-YFP构建体的表达在ECM中不与TGFBI相互作用和共定位。此外，与对照间皮来源的ECM相比，当铺在来源于缺乏紫杉醇的间皮细胞的ECM上时，卵巢癌细胞具有降低的运动性和降低的对化疗剂紫杉醇的响应。总之，TGF β 1通过一种新的相互作用调节TGFBI的纤维状ECM沉积，随后影响癌细胞行为。
TGFBI has been shown to sensitize ovarian cancer cells to the cytotoxic effects of paclitaxel via an integrin receptor-mediated mechanism that modulates microtubule stability. Herein, we determine that TGFBI localizes within organized fibrillar structures in mesothelial-derived ECM. We determined that suppression of SPARC expression by shRNA decreased the deposition of TGFBI in mesothelial-derived ECM, without affecting its overall protein expression or secretion. Conversely, overexpression of SPARC increased TGFBI deposition. A SPARC-YFP fusion construct expressed by the Met5a cell line co-localized with TGFBI in the cell-derived ECM. Interestingly, in vitro produced SPARC was capable of precipitating TGFBI from cell lysates dependent on an intact SPARC carboxy-terminus with in vitro binding assays verifying a direct interaction. The last 37 amino acids of SPARC were shown to be required for the TGFBI interaction while expression of a SPARC-YFP construct lacking this region (aa 1–256) did not interact and co-localize with TGFBI in the ECM. Furthermore, ovarian cancer cells have a reduced motility and decreased response to the chemotherapeutic agent paclitaxel when plated on ECM derived from mesothelial cells lacking SPARC compared to control mesothelial-derived ECM. In conclusion, SPARC regulates the fibrillar ECM deposition of TGFBI through a novel interaction, subsequently influencing cancer cell behavior.
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影响因子：
--
作者：
Beacham, Dorothy A;Amatangelo, Michael D;Cukierman, Edna
通讯作者：
Cukierman, Edna
影响因子：
4.7
作者：
Brown, TJ;Shaw, PA;Ringuette, MJ
通讯作者：
Ringuette, MJ
影响因子：
3.7
作者：
NIEDBALA, MJ;CRICKARD, K;BERNACKI, RJ
通讯作者：
BERNACKI, RJ
影响因子：
4.8
作者：
Barker, TH;Baneyx, G;Sage, EH
通讯作者：
Sage, EH
DOI：
10.1016/s0006-291x(02)00576-4
发表时间：
2002-06-28
影响因子：
3.1
作者：
Bae, JS;Lee, SH;Kim, IS
通讯作者：
Kim, IS