Shaw Aubie, Bushman Wade
McArdle Laboratory for Cancer Research and Department of Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
J Urol. 2007 Mar;177(3):832-8. doi: 10.1016/j.juro.2006.10.061.
Recent discoveries highlight the importance of the hedgehog signaling pathway in prostate growth regulation. We reviewed the role of hedgehog signaling in prostate development, adult prostate homeostasis and prostate cancer.
A comprehensive review of all relevant literature was done.
Epithelial expression of hedgehog ligand during prostate development exerts autocrine and paracrine signaling activities that regulate growth and differentiation. Hedgehog signaling also occurs in the adult human prostate but to our knowledge the influence on epithelial proliferation and/or differentiation is unknown. Robust hedgehog signaling occurs frequently in prostate cancer, and autocrine and paracrine signaling have been shown to accelerate the growth of xenograft tumors. Autocrine signaling has been implicated in stimulating stem/progenitor cells and increased hedgehog pathway activity may be a characteristic of advanced, androgen independent cancer. The plant alkaloid cyclopamine is a specific chemical inhibitor of hedgehog signaling that produced sustained regression of established xenograft tumors.
Hedgehog signaling has an important role in prostate development and it appears to be a characteristic feature of prostate cancer. It stimulates tumor growth and may exert a specific role in the proliferation of tumor stem cells. The development of hedgehog inhibitors based on the action of cyclopamine holds promise for novel treatments to slow or arrest tumor growth.
近期的研究发现突出了刺猬信号通路在前列腺生长调节中的重要性。我们综述了刺猬信号在前列腺发育、成年前列腺内环境稳定及前列腺癌中的作用。
对所有相关文献进行全面综述。
在前列腺发育过程中，刺猬信号配体的上皮表达发挥自分泌和旁分泌信号活性，调节生长和分化。刺猬信号在成年男性前列腺中也存在，但据我们所知，其对上皮增殖和/或分化的影响尚不清楚。刺猬信号在前列腺癌中频繁强烈激活，且自分泌和旁分泌信号已被证明可加速异种移植肿瘤的生长。自分泌信号与刺激干细胞/祖细胞有关，刺猬信号通路活性增加可能是晚期雄激素非依赖性癌症的一个特征。植物生物碱环杷明是刺猬信号的一种特异性化学抑制剂，可使已建立的异种移植肿瘤持续消退。
刺猬信号在前列腺发育中起重要作用，似乎是前列腺癌的一个特征。它刺激肿瘤生长，并可能在肿瘤干细胞增殖中发挥特定作用。基于环杷明作用开发的刺猬信号抑制剂有望成为减缓或阻止肿瘤生长的新型治疗方法。
