Understanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

了解神经毡蛋白 2 (NRP2) 在前列腺癌细胞以及骨微环境中的作用对于开发治疗前列腺癌骨转移的有效靶向疗法至关重要。我们观察到转移至骨的前列腺癌细胞中 NRP2 显着上调。在这里，我们报告说，靶向癌细胞中的 NRP2 可以增强基于紫杉烷的化疗，并在骨转移中获得更好的治疗效果，这表明 NRP2 是一个有前途的治疗靶点。由于肿瘤微环境中存在的破骨细胞表达 NRP2，因此我们研究了破骨细胞中靶向 NRP2 的潜在作用。我们的结果显示，在前列腺癌细胞存在的情况下，NRP2 负向调节破骨细胞的分化和功能，从而促进混合性骨病变。我们的研究进一步阐明了 NRP2 调节破骨细胞功能的分子机制。有趣的是，体内破骨细胞中 NRP2 的消耗表明骨中总体前列腺肿瘤负荷的减少。因此，这些结果表明，靶向前列腺癌细胞以及破骨细胞区室中的 NRP2 可有益于治疗前列腺癌骨转移。