Therapeutic Potential of a Novel αvβ3 Antagonist to Hamper the Aggressiveness of Mesenchymal Triple Negative Breast Cancer Sub-Type
Therapeutic Potential of a Novel αvβ3 Antagonist to Hamper the Aggressiveness of Mesenchymal Triple Negative Breast Cancer Sub-Type
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DOI：
10.3390/cancers11020139
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发表时间：
2019-02-01
期刊：
影响因子：
5.2
通讯作者：
Zannetti, Antonella
中科院分区：
文献类型：
--
作者：
Hill, Billy Samuel;Sarnella, Annachiara;Zannetti, Antonella
三阴性乳腺癌（MES-TNBC）的间质亚型由于其侵袭性和干细胞样特征而具有高度侵袭性行为和较差的预后，这与转移性播散和对治疗的耐药性相关。此外，MES-TNBC 的特点是表达与上皮间质转化 (EMT) 程序和癌症干细胞 (CSC) 相关的分子标记。 α(v)β(3) 整合素表达的改变已被确定为癌症进展、干性和转移的驱动因素。在这里，我们发现高水平的 alpha(v)beta(3) 与 MES-TNBC 相关，因此利用靶向该整合素的可能性来降低这种癌症的侵袭性。为此，我们用一种名为 psi RGDechi 的新型肽处理 MES-TNBC 细胞，该肽是我们最近开发的，并以其选择性结合和抑制 alpha(v)beta(3) 整合素的能力为特征。值得注意的是，psi RGDechi 能够阻碍 MES-TNBC 细胞的粘附、迁移和侵袭，以及这些细胞形成血管样结构和微球的能力。此外，这种肽可逆转 EMT 程序，抑制间充质标志物。这些发现表明，RGDechi 靶向 α(v)β(3) 整合素，有可能抑制 MES-TNBC 表型的一些恶性特性。
The mesenchymal sub-type of triple negative breast cancer (MES-TNBC) has a highly aggressive behavior and worse prognosis, due to its invasive and stem-like features, that correlate with metastatic dissemination and resistance to therapies. Furthermore, MES-TNBC is characterized by the expression of molecular markers related to the epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs). The altered expression of alpha(v)beta(3) integrin has been well established as a driver of cancer progression, stemness, and metastasis. Here, we showed that the high levels of alpha(v)beta(3) are associated with MES-TNBC and therefore exploited the possibility to target this integrin to reduce the aggressiveness of this carcinoma. To this aim, MES-TNBC cells were treated with a novel peptide, named psi RGDechi, that we recently developed and characterized for its ability to selectively bind and inhibit alpha(v)beta(3) integrin. Notably, psi RGDechi was able to hamper adhesion, migration, and invasion of MES-TNBC cells, as well as the capability of these cells to form vascular-like structures and mammospheres. In addition, this peptide reversed EMT program inhibits mesenchymal markers. These findings show that targeting alpha(v)beta(3) integrin by RGDechi, it is possible to inhibit some of the malignant properties of MES-TNBC phenotype.