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ErbB3的一种分泌型异构体可促进骨中骨连接蛋白的表达，并增强前列腺癌细胞的侵袭性。

A secreted isoform of ErbB3 promotes osteonectin expression in bone and enhances the invasiveness of prostate cancer cells.

作者信息

Chen Nanyue, Ye Xiang-Cang, Chu Khoi, Navone Nora M, Sage E Helene, Yu-Lee Li-Yuan, Logothetis Christopher J, Lin Sue-Hwa

机构信息

Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

出版信息

Cancer Res. 2007 Jul 15;67(14):6544-8. doi: 10.1158/0008-5472.CAN-07-1330.

DOI:10.1158/0008-5472.CAN-07-1330
PMID:17638862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2000837/
Abstract

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.

摘要

前列腺癌易于转移至骨骼，这促使我们及其他研究人员提出，前列腺癌细胞与骨骼之间的双向相互作用对于前列腺癌优先转移至骨骼至关重要。我们之前在患有前列腺癌并发生骨转移的男性患者的骨髓上清液样本中鉴定出一种ErbB3分泌异构体（p45-sErbB3），并且通过对人体组织标本进行免疫组织化学分析表明，p45-sErbB3在骨转移前列腺癌细胞中高表达。在此，我们表明，在Boyden小室侵袭试验中，p45-sErbB3刺激小鼠颅骨分泌能够增加前列腺癌细胞侵袭性的因子。利用基因阵列分析来鉴定p45-sErbB3反应性基因，我们发现p45-sErbB3上调了颅骨中骨连接蛋白/富含半胱氨酸的酸性分泌蛋白（osteonectin/SPARC）、双糖链蛋白聚糖（biglycan）和I型胶原蛋白的表达。我们进一步表明，重组骨连接蛋白增加了PC-3细胞的侵袭性，而骨连接蛋白中和抗体则阻断了这种p45-sErbB3诱导的侵袭性。这些结果表明，p45-sErbB3部分通过刺激骨骼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与骨骼之间的双向相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/36c01acb96f7/nihms27155f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/578373e41248/nihms27155f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/f0f50e8a21f2/nihms27155f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/36c01acb96f7/nihms27155f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/578373e41248/nihms27155f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/f0f50e8a21f2/nihms27155f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e55f/2000837/36c01acb96f7/nihms27155f3.jpg

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