Regulation of invasion of epithelial ovarian cancer by transforming growth factor-β
Regulation of invasion of epithelial ovarian cancer by transforming growth factor-β
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DOI：
10.1006/gyno.2000.6042
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发表时间：
2001-02-01
影响因子：
4.7
通讯作者：
Stack, MS
中科院分区：
文献类型：
--
作者：
Rodriguez, GC;Haisley, C;Stack, MS
Objective.上皮性卵巢癌的转移过程被认为涉及卵巢癌细胞的表面脱落和随后的传播，这是由卵巢癌细胞和腹膜表面之间界面处的局部蛋白水解促进的。然而，调节转移过程的因素还不清楚。转化生长因子-β（TGF-β）是一种多功能肽，其激发与转移过程相关的许多细胞效应。本研究旨在探讨TGF-β对卵巢癌转移的调节作用。我们评估了TGF-β对转移特性的影响，五种卵巢癌细胞系的粘附、侵袭、运动、蛋白水解（DOV-13和OVCA 420、429、432和433），两种短期原代卵巢癌细胞培养物（OVCA 10和OVCA 208）和五种正常卵巢表面上皮（NOSE）细胞培养物（OSE 133、185、186、188和189）。TGF-β对侵袭和蛋白水解的影响采用改良的Boyden室侵袭测定法、酶谱法、偶联比色活性测定法和基于HPLC的合成底物裂解定量法进行定量。TGF-β在7种卵巢癌细胞系中的5种中显著增加了侵袭，其数量范围为2至20倍。相比之下，TGF-β显著降低了5个NOSE分离株中的2个的侵袭性50%至80%，并且对3个分离株的侵袭性没有显著影响。TGF-β处理增加了OVCA 420和433以及DOV-13中的基质金属蛋白酶（MMP）表达，导致MMP依赖性胶原裂解和侵袭活性。MMP抑制剂GI 12947的加入中和了TGF-β对侵袭的增强作用。TGF-β对卵巢癌细胞的运动性没有影响，仅在DOV-13中增加粘附。这些数据表明，TGF-β可能通过诱导MMP活性增强卵巢癌的侵袭性。(C)北京：科学出版社.
Objective. The metastatic process in epithelial ovarian cancer is thought to involve surface shedding and subsequent dissemination of ovarian cancer cells, facilitated by localized proteolysis at the interface between ovarian cancer cells and peritoneal surfaces. The factors regulating the metastatic process, however, are not well understood. Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that elicits numerous cellular effects pertinent to the metastatic process. The purpose of this study was to evaluate the regulatory role of TGF-beta on metastasis in ovarian cancer.Methods. We evaluated the effect of TGF-beta on the metastatic characteristics (adhesion, invasion, motility, proteolysis) of five ovarian cancer cell lines (DOV-13 and OVCA 420, 429, 432, and 433), two short-term primary ovarian cancer cell cultures (OVCA 10 and OVCA 208), and five normal ovarian surface epithelial (NOSE) cell cultures (OSE 133, 185, 186, 188, and 189). The effect of TGF-beta on invasion and proteolysis was quantified using a modified Boyden chamber invasion assay, zymography, a coupled colorimetric activity assay, and an HPLC-based quantitation of synthetic substrate cleavage.Results. TGF-beta significantly increased invasion in five of seven ovarian cancer cell lines in amounts ranging from 2- to 20-fold. In contrast, TGF-beta significantly decreased invasion in two of five NOSE isolates by 50 to 80% and had no significant effect on invasion in three, TGF-beta treatment increased matrix metalloproteinase (MMP) expression in OVCA 420 and 433 and DOV-13, resulting in MMP-dependent collagen cleavage and invasive activity. Addition of the MMP inhibitor GI12947 neutralized the enhancing effect of TGF-beta on invasion. TGF-beta had no effect on ovarian cancer cell motility and only increased adhesion in DOV-13.Conclusions. These data suggest that TGF-beta may enhance the invasiveness of ovarian cancers through induction of MMP activity. (C) 2001 Academic Press.