Department of Nuclear Medicine, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany.
Department of Obstetrics and Gynecology, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany.
Cells. 2023 Feb 8;12(4):551. doi: 10.3390/cells12040551.
Recent studies proving prostate-specific membrane antigen (PSMA) expression on triple-negative breast cancer (TNBC) cells and adjacent endothelial cells suggest PSMA as a promising target for therapy of until now not-targetable cancer entities. In this study, PSMA and its isoform expression were analyzed in different TNBC cells, breast cancer stem cells (BCSCs), and tumor-associated endothelial cells. PSMA expression was detected in 91% of the investigated TNBC cell lines. The PSMA splice isoforms were predominantly found in the BCSCs. Tumor-conditioned media from two TNBC cell lines, BT-20 (high full-length PSMA expression, PSMAΔ18 expression) and Hs578T (low full-length PSMA expression, no isoform expression), showed significant pro-angiogenic effect with induction of tube formation in endothelial cells. All TNBC cell lines induced PSMA expression in human umbilical vein endothelial cells (HUVEC). Significant uptake of radiolabeled ligand [Ga]Ga-PSMA was detected in BCSC1 (4.2%), corresponding to the high PSMA expression. Moreover, hypoxic conditions increased the uptake of radiolabeled ligand [Lu]Lu-PSMA in MDA-MB-231 (0.4% vs. 3.4%, under hypoxia and normoxia, respectively) and MCF-10A (0.3% vs. 3.0%, under normoxia and hypoxia, respectively) significantly ( < 0.001). [Lu]Lu-PSMA-induced apoptosis rates were highest in BT-20 and MDA-MB-231 associated endothelial cells. Together, these findings demonstrate the potential of PSMA-targeted therapy in TNBC.
最近的研究证明，前列腺特异性膜抗原（PSMA）在三阴性乳腺癌（TNBC）细胞和相邻内皮细胞上的表达表明 PSMA 是治疗迄今为止无法靶向的癌症实体的有前途的靶点。在这项研究中，分析了不同的 TNBC 细胞、乳腺癌干细胞（BCSCs）和肿瘤相关内皮细胞中 PSMA 及其异构体的表达。在所研究的 TNBC 细胞系中，有 91%检测到 PSMA 表达。PSMA 剪接异构体主要存在于 BCSCs 中。来自两种 TNBC 细胞系 BT-20（高全长 PSMA 表达，PSMAΔ18 表达）和 Hs578T（低全长 PSMA 表达，无异构体表达）的肿瘤条件培养基显示出显著的促血管生成作用，可诱导内皮细胞管形成。所有 TNBC 细胞系均诱导人脐静脉内皮细胞（HUVEC）表达 PSMA。在 BCSC1 中检测到放射性标记配体[Ga]Ga-PSMA 的摄取显著（4.2%，对应于高 PSMA 表达）。此外，缺氧条件下 MDA-MB-231（分别为 0.4%和 3.4%，在缺氧和常氧条件下）和 MCF-10A（分别为 0.3%和 3.0%，在常氧和缺氧条件下）中放射性标记配体[Lu]Lu-PSMA 的摄取显著增加（<0.001）。BT-20 和 MDA-MB-231 相关内皮细胞中，[Lu]Lu-PSMA 诱导的细胞凋亡率最高。综上所述，这些发现表明 PSMA 靶向治疗在 TNBC 中的潜力。
