Correlation of tumor- and stromal-derived MT1-MMP expression with progression of human ovarian tumors in SCID mice
Correlation of tumor- and stromal-derived MT1-MMP expression with progression of human ovarian tumors in SCID mice
复制标题
DOI：
10.1016/j.ygyno.2004.08.032
复制
发表时间：
2004-12-01
影响因子：
4.7
通讯作者：
Thompson, EW
中科院分区：
文献类型：
--
作者：
Drew, AF;Blick, TJ;Thompson, EW
目标。将人卵巢癌标本原位移植到SCID小鼠体内，研究基质金属蛋白酶(MMPs)在卵巢肿瘤扩散中的作用。小鼠接种了患者肿瘤样本，在16周的时间里发生了卵巢肿瘤，其中一些小鼠发生了转移。采用物种特异性定量RT-PCR方法鉴定肿瘤相关基质金属蛋白酶的来源。膜型(MT)1-MMPmRNA在高级别肿瘤、有浆膜侵犯的肿瘤和有远处转移的肿瘤中显著增加。MT1-基质金属蛋白酶表达的增加主要来自人类肿瘤细胞，来自小鼠卵巢间质的贡献很小。人和小鼠的MT2-MMPs与肿瘤进展无关，而MT3-MMP值可以忽略不计。虽然肿瘤细胞不会产生大量的基质金属蛋白酶-2或基质金属蛋白酶-9，但肿瘤的存在与小鼠卵巢基质中基质金属蛋白酶-2表达水平的升高有关。间质来源的MT1-MMP值在大肿瘤中较大，且与间质MMP2的表达相关，但两者与转移均无明显关联。这些研究表明，与其他明胶溶解MMPs相比，肿瘤来源的MT1-MMPs与侵袭性肿瘤行为密切相关。该人卵巢癌原位模型适用于研究卵巢肿瘤的进展，对进一步研究卵巢癌的转移过程具有重要意义。(C)2004 Elsevier Inc.保留所有权利。
Objective. Human ovarian carcinoma samples were orthotopically implanted into SCID mice to investigate the contribution of matrix metalloproteases (MMPs) to the spread of ovarian tumors.Methods. Mice were inoculated with patient tumor samples, and developed ovarian tumors over a 16-week period with metastasis occurring in some mice. Species-specific quantitative RT-PCR was used to identify the source of tumor-associated MMPs.Results. Membrane-type (MT)1-MMP mRNA was significantly increased in high-grade tumors, tumors with evidence of serosal involvement, and tumors in which distant metastases were detected. The increase in MT1-MMP expression was predominantly from the human tumor cells, with a minor contribution from the mouse ovarian stroma. Neither human nor mouse MT2-MMP were correlated with tumor progression and MT3-MMP levels were negligible. While tumor cells did not produce significant amounts of MMP-2 or MMP-9, the presence of tumor was associated with increased levels of MMP-2 expression by mouse ovarian stroma. Stromal-derived MT1-MMP was greater in large tumors and was associated with stromal MMP-2 expression but neither was significantly linked with metastasis.Conclusions. These studies indicate that tumor-derived MT1-MMP, more so than other gelatinolytic MMPs, is strongly linked to aggressive tumor behavior. This orthotopic model of human ovarian carcinoma is appropriate for studying ovarian tumor progression, and will be valuable in the further investigation of the metastatic process. (C) 2004 Elsevier Inc. All rights reserved.