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首页> 外文期刊>Oncogene >A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation
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A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation

机译：前列腺癌细胞分泌的45 kDa ErbB3促进骨形成

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摘要

ErbB3 is a transmembrane growth factor receptor that has been implicated in the pathogenesis of human cancer. After finding that a truncated form of ErbB3 was present and upregulated in metastatic prostate cancer cells in lymph nodes and bone, we explored the pathophysiological functions of this unusual form of ErbB3 in the context of mouse calvaria as well as osteoblasts in vitro and the femur microenvironment in vivo. Here we demonstrate that prostate cancer cells expressed an alternatively spliced transcript that encodes a 45-kDa glycosylated protein (p45-sErbB3). The recombinant p45-sErbB3 purified from conditioned medium stimulated calvarial bone formation and induced osteoblast differentiation. Overexpression of p45-sErbB3 in the osteolytic prostate cancer cell line PC-3 converted its phenotype from bone lysing to bone forming upon injection into the femurs of immunodeficient mice. Further, we detected sErbB3 in plasma samples from patients with castration-resistant prostate cancer with bone metastasis. These observations establish that p45-sErbB3 is a structurally and functionally unique gene product of ErbB3 and suggest that p45-sErbB3 is likely one of the factors involved in the osteoblastic bone metastases of prostate cancer.
机译：ErbB3是跨膜生长因子受体，已与人类癌症的发病机制有关。发现淋巴结和骨骼的转移性前列腺癌细胞中存在并上调了ErbB3的截短形式后，我们探讨了这种异常形式的ErbB3在小鼠颅骨以及成骨细胞体外和股骨微环境中的病理生理功能。体内。在这里，我们证明前列腺癌细胞表达编码45 kDa糖基化蛋白（p45-sErbB3）的选择性剪接转录本。从条件培养基中纯化的重组p45-sErbB3刺激颅盖骨的形成并诱导成骨细胞分化。在溶骨性前列腺癌细胞系PC-3中过表达p45-sErbB3，可将其表型从溶骨转变为向免疫缺陷小鼠股骨注射后形成的骨形成。此外，我们从去势抵抗性前列腺癌骨转移患者的血浆样品中检测到sErbB3。这些观察结果证实p45-sErbB3是ErbB3的结构和功能上独特的基因产物，并表明p45-sErbB3可能是前列腺癌成骨骨转移中涉及的因素之一。

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