迫切需要更好地了解导管原位癌（DCIS），以将这些浸润前病变识别为不同的临床实体。 Semaphorin 3F (SEMA3F) 是一种可溶性轴突引导分子，其辅助受体 Neuropilin 1 (NRP1) 和 NRP2 在侵袭性上皮 BC 细胞中强烈表达。我们利用两种细胞系模型来代表从健康状态到轻度侵袭性的进展或导管原位癌（DCIS）阶段，并最终发展为侵袭性细胞系。此外，我们采用体内模型并对患者数据库进行分析，以确保我们结果的转化相关性。我们发现 SEMA3F 通过以下作用在乳腺癌 (BC) 的 DCIS 向浸润性导管癌转变过程中作为侵袭促进剂： NRP1 和 NRP2。在上皮细胞中，SEMA3F 激活上皮间质转化，同时促进细胞外基质降解以及基底膜和肌上皮细胞层分解。结合我们的患者数据库数据，这些概念验证结果揭示了最常见的侵袭前病变中发生的新的 SEMA3F 介导机制。 BC 病变、DCIS 代表其向侵袭转变的有效且直接的激活。此外，与临床和治疗相关的是，SEMA3F 的作用可以通过其辅助受体直接阻断，从而防止侵袭并将 DCIS 病变保持在侵袭前状态。© 2024。作者。

A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.© 2024. The Author(s).