The Potential of PSMA as a Vascular Target in TNBC

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Abstract

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 [68Ga]Ga-PSMA was detected in BCSC1 (4.2%), corresponding to the high PSMA expression. Moreover, hypoxic conditions increased the uptake of radiolabeled ligand [177Lu]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 (p < 0.001). [177Lu]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.

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Heesch, A., Ortmanns, L., Maurer, J., Stickeler, E., Sahnoun, S. E. M., Mottaghy, F. M., & Morgenroth, A. (2023). The Potential of PSMA as a Vascular Target in TNBC. Cells, 12(4). https://doi.org/10.3390/cells12040551

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