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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Secretion of pleiotrophin stimulates breast cancer progression through remodeling of the tumor microenvironment
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Secretion of pleiotrophin stimulates breast cancer progression through remodeling of the tumor microenvironment

机译：促肾上腺皮质激素的分泌通过肿瘤微环境的重塑刺激乳腺癌的进展

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Pleiotrophin (PTN, Ptn) is an 18-kDa secretory cytokine expressed in many breast cancers; however, the significance of Ptn expression in breast cancer has not been established. We have now tested three models to determine the role of inappropriate expression of Ptn in breast cancer. Mouse mammary tumor virus (MMTV) promoter-driven Ptn expressed in MMTV-polyoma virus middle T antigen (PyMT)-Ptn mouse breast cancers was first shown to induce rapid growth of morphologically identified foci of "scir-rhous" carcinoma and to extensively remodel the microenvironment, including increased tumor angiogenesis and striking increases in mouse protocollagens Iα2, IVα5, and XIα1, and elastin. Ectopic Ptn expression in MCF-7 (human breast cancer)-Ptn cell xenografts also was shown to markedly increase MCF-7-Ptn cell xenograft growth in nude mice; furthermore, it induced extensive remodeling of the microenvironment and tumor angiogenesis. In a coculture model of equal numbers of NIH 3T3 stromal fibroblasts and MCF-7-Ptn cells, PTN secreted from MCF-7-Ptn cells was then shown to induce a more malignant MCF-7-Ptn breast cancer cell phenotype and extensive remodeling of the MCF-7-Ptn/NIH 3T3 cell microenvironment; it up-regulated expression of markers of aggressive breast cancers, including PKCδ and matrix metalloproteinase-9 in both MCF-7-Ptn and NIH 3T3 cells. The morphological phenotypes of MCF-7-Ptn cell xenografts and MCF-7-Ptn cell/NIH 3T3 cell cocultures closely resembled breast cancers in MMTV-PyMT-Ptn mice. Inappropriate expression of Ptn thus promotes breast cancer progression in mice; the data suggest that secretion of PTN through stimulation of the stromal cell microenvironment alone may be sufficient to account for significant features of breast cancer progression.
机译：促营养素（PTN，Ptn）是一种在许多乳腺癌中表达的18 kDa分泌细胞因子。然而，尚未确定Ptn表达在乳腺癌中的重要性。现在，我们已经测试了三种模型，以确定Ptn的不适当表达在乳腺癌中的作用。在MMTV-多瘤病毒中T抗原（PyMT）-Ptn小鼠乳腺癌中表达的小鼠乳腺肿瘤病毒（MMTV）启动子驱动的Ptn首次显示可诱导“ scir-rhous”癌的形态学鉴定灶快速生长并广泛重塑微环境，包括增加的肿瘤血管生成和小鼠协议中显着增加的lagensIα2，IVα5和XIα1和弹性蛋白。 MCF-7（人乳腺癌）-Ptn细胞异种移植物中的异位Ptn表达也显示出显着增加裸鼠中MCF-7-Ptn细胞异种移植的生长。此外，它诱导了微环境的广泛重塑和肿瘤血管生成。在同等数量的NIH 3T3基质成纤维细胞和MCF-7-Ptn细胞的共培养模型中，从MCF-7-Ptn细胞分泌的PTN被显示出可诱导更恶性的MCF-7-Ptn乳腺癌细胞表型和广泛的重塑MCF-7-Ptn / NIH 3T3细胞微环境；它上调了MCF-7-Ptn和NIH 3T3细胞中侵袭性乳腺癌标志物的表达，包括PKCδ和基质金属蛋白酶9。 MCF-7-Ptn细胞异种移植物和MCF-7-Ptn细胞/ NIH 3T3细胞共培养物的形态表型与MMTV-PyMT-Ptn小鼠的乳腺癌极为相似。因此，Ptn表达不当会促进小鼠乳腺癌的发展。数据表明，仅通过刺激基质细胞微环境而分泌PTN可能足以说明乳腺癌进展的重要特征。

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