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The Potential of PSMA as a Vascular Target in TNBC
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 ana...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954547/ https://www.ncbi.nlm.nih.gov/pubmed/36831218 http://dx.doi.org/10.3390/cells12040551 |
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author | Heesch, Amelie Ortmanns, Lars Maurer, Jochen Stickeler, Elmar Sahnoun, Sabri E. M. Mottaghy, Felix M. Morgenroth, Agnieszka |
author_facet | Heesch, Amelie Ortmanns, Lars Maurer, Jochen Stickeler, Elmar Sahnoun, Sabri E. M. Mottaghy, Felix M. Morgenroth, Agnieszka |
author_sort | Heesch, Amelie |
collection | PubMed |
description | 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 [(68)Ga]Ga-PSMA was detected in BCSC1 (4.2%), corresponding to the high PSMA expression. Moreover, hypoxic conditions increased the uptake of radiolabeled ligand [(177)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 (p < 0.001). [(177)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. |
format | Online Article Text |
id | pubmed-9954547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99545472023-02-25 The Potential of PSMA as a Vascular Target in TNBC Heesch, Amelie Ortmanns, Lars Maurer, Jochen Stickeler, Elmar Sahnoun, Sabri E. M. Mottaghy, Felix M. Morgenroth, Agnieszka Cells Article 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 [(68)Ga]Ga-PSMA was detected in BCSC1 (4.2%), corresponding to the high PSMA expression. Moreover, hypoxic conditions increased the uptake of radiolabeled ligand [(177)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 (p < 0.001). [(177)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. MDPI 2023-02-08 /pmc/articles/PMC9954547/ /pubmed/36831218 http://dx.doi.org/10.3390/cells12040551 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Heesch, Amelie Ortmanns, Lars Maurer, Jochen Stickeler, Elmar Sahnoun, Sabri E. M. Mottaghy, Felix M. Morgenroth, Agnieszka The Potential of PSMA as a Vascular Target in TNBC |
title | The Potential of PSMA as a Vascular Target in TNBC |
title_full | The Potential of PSMA as a Vascular Target in TNBC |
title_fullStr | The Potential of PSMA as a Vascular Target in TNBC |
title_full_unstemmed | The Potential of PSMA as a Vascular Target in TNBC |
title_short | The Potential of PSMA as a Vascular Target in TNBC |
title_sort | potential of psma as a vascular target in tnbc |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954547/ https://www.ncbi.nlm.nih.gov/pubmed/36831218 http://dx.doi.org/10.3390/cells12040551 |
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