SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix
SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix
复制标题
DOI：
10.1002/ijc.21357
复制
发表时间：
2006-01-15
影响因子：
6.4
通讯作者：
Cohn, SL
中科院分区：
文献类型：
--
作者：
Chlenski, A;Liu, SQ;Cohn, SL
分泌蛋白，酸性且富含半胱氨酸（SPARC），是一种多功能的基质细胞糖蛋白。在体外，SPARC具有抗血管生成特性，包括能够抑制bFGF和VEGF刺激的内皮细胞的增殖和迁移。先前，我们证明了血小板来源的SPARC也抑制血管生成并损害神经母细胞瘤肿瘤的体内生长。在本研究中，我们在转化的人胚胎肾细胞系293中产生了rhSPARC，并表明重组分子保留了其抑制血管生成的能力。尽管体外实验中外源性SPARC表达不影响293细胞的增殖，但与野生型细胞或转染对照载体的293细胞组成的肿瘤相比，SPARC转染293细胞形成的肿瘤生长明显受损。与sparc作为血管生成抑制剂的功能一致，在sparc转染的293肿瘤中，与对照组相比，血管明显减少，并且这些肿瘤中凋亡细胞的数量增加。光镜下显示，在SPARC表达的异种移植物中，肿瘤细胞的小巢被丰富的间质组织包围，而对照肿瘤主要由缺乏间质组织的肿瘤细胞组成。在sparc转染的293异种移植物中检测到成熟的共价交联胶原，但在对照肿瘤中未检测到。我们的研究表明，SPARC可能通过抑制血管生成、诱导肿瘤细胞凋亡和调节肿瘤微环境沉积和组织的变化来调节肿瘤生长。(c) 2005 Wiley-Liss, Inc。
Secreted protein, acidic and rich in cysteine (SPARC), is a multifunctional matricellular glycoprotein. In vitro, SPARC has antiangiogenic properties, including the ability to inhibit the proliferation and migration of endothelial cells stimulated by bFGF and VEGF. Previously, we demonstrated that platelet-derived SPARC also inhibits angiogenesis and impairs the growth of neuroblastoma tumors in vivo. In the present study, we produced rhSPARC in the transformed human embryonic kidney cell line 293 and show that the recombinant molecule retains its ability to inhibit angiogenesis. Although 293 cell proliferation was not affected by exogenous expression of SPARC in vitro, growth of tumors formed by SPARC-transfected 293 cells was significantly impaired compared to tumors comprised of wild-type cells or 293 cells transfected with a control vector. Consistent with its function as an angiogenesis inhibitor, significantly fewer blood vessels were seen in SPARC-transfected 293 tumors compared to controls, and these tumors contained increased numbers of apoptotic cells. Light microscopy revealed small nests of tumor cells surrounded by abundant stromal tissue in xenografts with SPARC expression, whereas control tumors were comprised largely of neoplastic cells with scant stroma. Mature, covalently cross-linked collagen was detected in SPARC-transfected 293 xenografts but not in control tumors. Our studies suggest that SPARC may regulate tumor growth by inhibiting angiogenesis, inducing tumor cell apoptosis and mediating changes in the deposition and organization of the tumor microenvironment. (c) 2005 Wiley-Liss, Inc.