Liu Xiao, Tan Weiwei, Wang Weiqi, Feng Tingting, Wang Chunni, Wang Lin, Zhou Wei
Department of Oncology, Zibo Central Hospital, Zibo, China.
Department of Pathology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.
J Cancer. 2023 Aug 21;14(14):2633-2643. doi: 10.7150/jca.86739. eCollection 2023.
Semaphorin 4A (SEMA4A) belonged to a family of membrane-bound proteins that were initially recognized as a kind of axon guidance factors in nervous system. It was preferentially expressed on immune cells and has been proven to play a prominent role in immune function and angiogenesis. In this study, we found that SEMA4A was highly expressed in prostate cancer (PCa) tissues and correlated with Gleason scores and distant metastasis. SEMA4A could induce Epithelial-mesenchymal transition (EMT) of PCa cells and consequently promote invasion by establishing a positive loop with IL-10 in stromal cells. experiments showed more dissemination in mice injected with SEMA4A-overexpressing cells in mouse models and both the number and size of lung metastases were significantly increased in SEMA4A-overexpressing tumors. SEMA4A depletion by genetic means prevents lung metastasis in PCa xenograft models. Our data suggest a crucial role of SEMA4A in PCa and blocking SEMA4A-IL-10 axis represents an attractive approach to improving therapeutic outcomes.
信号素4A（SEMA4A）属于膜结合蛋白家族，最初被认为是神经系统中的一种轴突导向因子。它在免疫细胞上优先表达，并且已被证明在免疫功能和血管生成中发挥重要作用。在本研究中，我们发现SEMA4A在前列腺癌（PCa）组织中高表达，且与Gleason评分和远处转移相关。SEMA4A可诱导PCa细胞发生上皮-间质转化（EMT），并通过与基质细胞中的白细胞介素-10建立正反馈回路从而促进侵袭。实验表明，在小鼠模型中，注射过表达SEMA4A细胞的小鼠有更多的播散，且在过表达SEMA4A的肿瘤中，肺转移灶的数量和大小均显著增加。通过基因手段耗尽SEMA4A可防止PCa异种移植模型中的肺转移。我们的数据表明SEMA4A在PCa中起关键作用，阻断SEMA4A-白细胞介素-10轴是改善治疗效果的一种有吸引力的方法。
