雄激素和雄激素受体 (AR) 介导的信号通路对于前列腺发育、形态发生、生长和再生至关重要。早期组织重组实验表明，AR缺陷的泌尿生殖窦间充质与完整的泌尿生殖窦上皮结合未能发育成前列腺，这表明间充质AR在前列腺发育中存在干细胞生态位。雄激素信号传导对于产后阶段前列腺的成熟和生长仍然至关重要。重要的是，大多数原发性前列腺癌 (PCa) 细胞表达 AR，AR 的异常激活直接促进 PCa 的发育、生长和进展。因此，针对PCa细胞中AR的雄激素剥夺疗法（ADT）是晚期PCa的主要治疗方法。然而，它最终失败了，导致了去势抵抗性前列腺癌的发展，这是一种不治之症。鉴于这些临床挑战，需要重新评估致癌 AR 作用，以开发新的有效疗法。最近，基质 AR 在调节前列腺发育和肿瘤发生中的重要作用被确定。在这里，我们总结了基质 AR 生态位及其与前列腺上皮细胞相互作用的最新发现。结合新出现的临床和实验证据，我们特别讨论了有关基质 AR 的肿瘤利基作用的几个重要且长期未解答的问题，并强调了通过共同靶向上皮和基质 AR 来治疗晚期 PCa 的未来治疗策略。© 2024。作者（s）。

Androgens and androgen receptor (AR) mediated signaling pathways are essential for prostate development, morphogenesis, growth, and regeneration. Early tissue recombination experiments showed that AR-deficient urogenital sinus mesenchyme combined with intact urogenital sinus epithelium failed to develop into a prostate, demonstrating a stem cell niche for mesenchymal AR in prostatic development. Androgen signaling remains critical for prostate maturation and growth during postnatal stages. Importantly, most primary prostate cancer (PCa) cells express the AR, and aberrant activation of AR directly promotes PCa development, growth, and progression. Therefore, androgen deprivation therapy (ADT) targeting the AR in PCa cells is the main treatment for advanced PCa. However, it eventually fails, leading to the development of castration-resistant PCa, an incurable disease. Given these clinical challenges, the oncogenic AR action needs to be reevaluated for developing new and effective therapies. Recently, an essential niche role of stromal AR was identified in regulating prostate development and tumorigenesis. Here, we summarize the latest discoveries of stromal AR niches and their interactions with prostatic epithelia. In combination with emerging clinical and experimental evidence, we specifically discuss several important and long-term unanswered questions regarding tumor niche roles of stromal AR and highlight future therapeutic strategies by co-targeting epithelial and stromal AR for treating advanced PCa.© 2024. The Author(s).