Tumor budding (TB) is considered a histomorphological marker of poor prognosis in patients with breast cancer (BC). Tumor vasculature is disordered and unstable in BC, which causes restricted drug delivery, hypoxia, and tumor metastasis. Traditional anti-angiogenic treatments cause extreme hypoxia, increased invasion, metastasis, and drug resistance due to blood vessel rarefaction or regression. Therefore, the application of anti-angiogenic strategies for vascular normalization in tumors is crucial to improve therapeutic efficacy in BC. In the present study, we found that transgelin (TAGLN) promoted the normalization of tumor vessels by regulating the structure and function of endothelial cells, and knockout of TAGLN in tumor-bearing mice resulted in tumor vessel abnormalization, an increase in epithelial-mesenchymal transition characteristics of tumor cells, and promotion of TB. Moreover, BC cells secrete exosomal miR-22-3p that mediates tumor vessel abnormalization by inhibiting TAGLN. We demonstrated for the first time that TAGLN plays an essential role in tumor vessel normalization, and thus it impairs TB and metastasis. Additionally, the findings of this study indicate that exosomal miR-22-3p is a potential therapeutic target for BC.

肿瘤出芽 (TB) 被认为是乳腺癌 (BC) 患者预后不良的组织形态学标志物。BC中肿瘤血管系统紊乱且不稳定，导致药物输送受限、缺氧和肿瘤转移。传统的抗血管生成治疗由于血管稀疏或退化导致极度缺氧、侵袭、转移和耐药性增加。因此，在肿瘤血管正常化中应用抗血管生成策略对于提高 BC 的治疗效果至关重要。在本研究中，我们发现转运蛋白 (TAGLN) 通过调节内皮细胞的结构和功能促进肿瘤血管的正常化，并且在荷瘤小鼠中敲除 TAGLN 导致肿瘤血管异常，增加肿瘤细胞的上皮-间质转化特性，促进结核。此外，BC 细胞分泌外泌体 miR-22-3p，通过抑制 TAGLN 介导肿瘤血管异常。我们首次证明 TAGLN 在肿瘤血管正常化中起着重要作用，因此它会损害 TB 和转移。此外，这项研究的结果表明外泌体 miR-22-3p 是 BC 的潜在治疗靶点。