A secreted isoform of ErbB3 promotes osteonectin expression in bone and enhances the invasiveness of prostate cancer cells
A secreted isoform of ErbB3 promotes osteonectin expression in bone and enhances the invasiveness of prostate cancer cells
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DOI：
10.1158/0008-5472.can-07-1330
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发表时间：
2007-07-15
期刊：
影响因子：
11.2
通讯作者：
Lin, Sue-Hwa
中科院分区：
文献类型：
--
作者：
Chen, Nanyue;Ye, Xiang-Cang;Lin, Sue-Hwa
前列腺癌转移到骨的倾向使我们和其他人提出，前列腺癌细胞和骨之间的双向相互作用对于前列腺癌优先转移到骨至关重要。我们之前在患有前列腺癌和骨转移的男性的骨髓上清液样本中鉴定出 ErbB3 (p45-sErbB3) 的分泌亚型，并通过对人体组织样本的免疫组织化学分析表明，p45-sErbB3 在骨中的转移性前列腺癌细胞中高表达。在这里，我们在博伊登室侵袭试验中表明，p45-sErbB3 刺激小鼠颅盖分泌增加前列腺癌细胞侵袭性的因子。使用基因阵列分析来鉴定 p45-sErbB3 反应基因，我们发现 p45-sErbB3 上调颅骨中骨连接蛋白/SPARC、双糖链蛋白聚糖和 I 型胶原的表达。我们进一步表明，重组骨连蛋白增加了 PC-3 细胞的侵袭性，而骨连蛋白中和抗体则阻断了 p45-sErbB3 诱导的侵袭性。这些结果表明p45-sErbB3部分通过刺激骨分泌骨连接蛋白来增强PC-3细胞的侵袭性。因此，p45-sErbB3可能通过骨连接蛋白介导前列腺癌细胞和骨之间的双向相互作用。
The propensity for prostate cancer to metastasize to bone led us and others to propose that bidirectional interactions between prostate cancer cells and bone are critical for the preferential metastasis of prostate cancer to bone. We identified previously a secreted isoform of ErbB3 (p45-sErbB3) in bone marrow supernatant samples from men with prostate cancer and bone metastasis and showed by immunohistochemical analysis of human tissue specimens that p45-sErbB3 was highly expressed in metastatic prostate cancer cells in bone. Here, we show that p45-sErbB3 stimulated mouse calvaria to secrete factors that increased the invasiveness of prostate cancer cells in a Boyden chamber invasion assay. Using gene array analysis to identify p45-sErbB3-responsive genes, we found that p45-sErbB3 up-regulated the expression of osteonectin/SPARC, biglycan, and type I collagen in calvaria. We further show that recombinant osteonectin increased the invasiveness of PC-3 cells, whereas osteonectin-neutralizing antibodies blocked this p45-sErbB3-induced invasiveness. These results indicate that p45-sErbB3 enhances the invasiveness of PC-3 cells in part by stimulating the secretion of osteonectin by bone. Thus, p45-sErbB3 may mediate the bidirectional interactions between prostate cancer cells and bone via osteonectin.