PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells
PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells
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DOI：
10.1093/carcin/bgh171
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发表时间：
2004-09-01
期刊：
影响因子：
4.7
通讯作者：
Serrero, G
中科院分区：
文献类型：
--
作者：
Tangkeangsirisin, W;Serrero, G
转移是一个多步骤的过程，乳腺癌进展为预后不良的疾病。生长因子和/或生长因子受体的过度表达已被报道在这一过程中发挥重要作用。88 kDa糖蛋白PC细胞衍生生长因子(PCDGF/GP88)，又称原颗粒蛋白，已被证明在乳腺肿瘤的发生发展中起重要作用，它通过刺激增殖、介导生存和对他莫昔芬产生耐药而发挥重要作用。本研究旨在探讨PCDGF/GP88在乳腺癌中的转移潜能。利用MCF-7细胞，我们发现PCDGF/GP88过表达促进了细胞的贴壁依赖性生长，并通过Matrigel加速了细胞的迁移。用PCDGF/GP88外源性处理MCF-7细胞也得到了类似的结果。此外，明胶酶谱和免疫印迹显示PCDGF/GP88上调了基质金属蛋白酶-9的表达。PCDGF/GP88可刺激MCF-7细胞表达血管内皮生长因子。这些结果表明，PCDGF/GP88除了能促进乳腺癌细胞的增殖和存活外，还能促进癌细胞的转移和血管生成。
Metastasis is a multi-step process involved in the progression of breast cancer to a disease with poor prognosis. Growth factor and/or growth factor receptor over- expression have been reported to play an important role in this process. The 88 kDa glycoprotein PC cell-derived growth factor (PCDGF/GP88), also known as progranulin, has been shown to play a major role in breast tumorigenesis by stimulating proliferation, mediating survival and conferring resistance to tamoxifen. In the present paper, the metastatic potential of PCDGF/GP88 was examined in breast cancer. Using MCF-7 cells, we showed that PCDGF/GP88 over-expression stimulated anchorage-independent cell growth and accelerated cell migration through matrigel. Similar results were obtained with MCF-7 cells treated exogenously with PCDGF/GP88. Furthermore, gelatin zymograph and immunoblot revealed that matrix metalloprotease-9 was up-regulated by PCDGF/GP88. PCDGF/GP88 stimulated VEGF expression in MCF-7 cells. These results suggest that PCDGF/GP88 could act to promote metastasis and angiogenesis in human breast cancer cells in addition to stimulating their proliferation and survival.