Triple-negative breast cancer (TNBC) that lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is a breast cancer subtype with very aggressive metastasis and poor prognosis. Unique cartilage matrix-associated protein (UCMA) is a vitamin K-dependent protein (VKDP) with a high-density γ-carboxyglutamic acid (Gla) domain due to the action of vitamin K. UCMA promotes osteoblast differentiation and mineral deposition in bone and suppresses calcification in vessels. However, correlation between UCMA and TNBC is unknown. This study investigated the inhibitory effect of UCMA on TNBC cell in vitro migration, invasion, and colony formation in addition to in vivo tumorigenesis. Cell migration and invasion significantly decreased in Ucma-overexpressing MDA-MB-231 and 4T1 cells compared to the mock control cells. Also, colony formation and the number of colonies significantly decreased in Ucma-overexpressing MDA-MB-231 and 4T1 cells. These results indicate that UCMA significantly inhibits the migration, invasion, and colony formation of TNBC cells. In an in vivo xenograft mouse model, tumor growth significantly decreased in mice bearing Ucma-overexpressing TNBC cells compared to the mock control cells, indicating that UCMA reduced in vivo tumor growth, similar to the inhibitory role of UCMA in vitro. Survival analysis using publicly available database showed that high UCMA expression significantly correlated with favorable relapse-free survival in TNBC patients compared to those with the other VKDPs, matrix Gla protein (MGP) and osteocalcin (OCN). Collectively, this study suggests that UCMA is a promising new therapeutic agent for TNBC.

缺乏雌激素受体（ER），孕激素受体（PR）和人表皮生长因子受体2（HER2）表达的三阴性乳腺癌（TNBC）是转移性非常强且预后不良的乳腺癌亚型。独特的软骨基质相关蛋白（UCMA）是维生素K依赖性蛋白（VKDP），由于维生素K的作用，具有高密度的γ-羧基谷氨酸（Gla）结构域。UCMA促进成骨细胞的分化和骨骼中矿物质的沉积抑制血管钙化。但是，UCMA和TNBC之间的相关性未知。这项研究调查了UCMA对TNBC细胞的体外迁移，侵袭和集落形成的抑制作用以及体内作用肿瘤发生。与模拟对照细胞相比，在过表达Ucma的MDA-MB-231和4T1细胞中，细胞迁移和侵袭显着降低。同样，在过表达Ucma的MDA-MB-231和4T1细胞中，菌落形成和菌落数量显着减少。这些结果表明，UCMA显着抑制TNBC细胞的迁移，侵袭和集落形成。在体内异种移植小鼠模型中，与模拟对照细胞相比，带有过表达Ucma的TNBC细胞的小鼠的肿瘤生长显着减少，这表明UCMA降低了体内肿瘤的生长，类似于UCMA在体外的抑制作用。。使用公开数据库进行的生存分析显示，与其他VKDP，基质Gla蛋白（MGP）和骨钙素（OCN）相比，TNBC患者的UCMA高表达与良好的无复发生存显着相关。总体而言，这项研究表明UCMA是有希望的TNBC新治疗剂。