Tumorigenic potential of extracellular matrix metalloproteinase inducer
Tumorigenic potential of extracellular matrix metalloproteinase inducer
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DOI：
10.1016/s0002-9440(10)64660-3
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发表时间：
2001-06-01
影响因子：
6
通讯作者：
Toole, BP
中科院分区：
文献类型：
--
作者：
Zucker, S;Hymowitz, M;Toole, BP
细胞外基质金属蛋白酶诱导物（EMMPRIN）是一种存在于癌细胞质膜上的糖蛋白，可促进成纤维细胞合成基质金属蛋白酶（MMPs）。肿瘤周围成纤维细胞合成人类肿瘤中大部分MMPs而不是癌细胞本身的证据已经点燃了对EMMPRIN在肿瘤扩散中作用的兴趣。在这份报告中，我们已经证明了EMMPRIN在癌症进展中的作用。用EMMPRIN cDNA转染人MDA-MB-436乳腺癌细胞（致瘤性但体内生长缓慢），并原位注射到雌性NCr nu/nu小鼠的乳腺组织中。绿色荧光蛋白用于可视化转移。在三个实验中，转染EMMPRIN cDNA的乳腺癌细胞克隆比质粒转染的癌细胞具有更高的致瘤性和侵袭性。明胶酶A和明胶酶B表达增加（通过原位杂交和明胶底物酶谱法证实）在EMMPRIN增强的肿瘤中得到证实。与人类的新生乳腺癌相比，人类肿瘤移植到小鼠中引起最小的基质或炎性细胞反应。基于这些实验研究和我们以前的证明，EMMPRIN是突出显示在人类癌症组织中，我们提出，EMMPRIN起着重要的作用，在癌症的进展，通过增加MMP的合成。
Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors, In contrast to ne novo breast canters in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs.