Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases

Kasoha, Mariz; Unger, C.; Solomayer, Erich‐Franz; Bohle, Rainer M.; Zaharia, Claudia; Khreich, Fadi; Wagenpfeil, Stefan; Juhasz‐Böss, I.

doi:10.1007/s10585-018-9878-x

Cited by 64 publications

(60 citation statements)

References 39 publications

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“…Kasoha et al, reported PSMA expression in healthy breast tissue only on normal glandular cells, while tumorous tissue as well as its metastases showed PSMA expression in tumor cells and in tumor associated neovasculature. Moreover, they confirmed higher PSMA expression in neovasculature of distant metastases than in those of primary tumors [ 26 ]. These findings are also supported by others, reporting PSMA as being highly and specifically expressed in the tumor neovasculature of ovarian, cervical and endometrial cancer [ 27 ].…”

Section: Discussionmentioning

confidence: 94%

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival

Traub‐Weidinger

Poetsch

Wöehrer

et al. 2021

JPM

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Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-11C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients’ survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.

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Section: Discussionmentioning

confidence: 94%

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival

Traub‐Weidinger

Poetsch

Wöehrer

et al. 2021

JPM

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“…Kasoha et al, observed PSMA to be expressed in the neovasculature of breast tumors and its distant metastases. Interestingly, the 68 Ga-PSMA tracer was strongly uptaken in the bone metastases of a metastatic BC patients, elucidating PSMA as a therapeutic vascular target (10). In the management of PCA, PSMA has already become an attractive target for oncological imaging and radionuclide therapy since its expression persisted in a high percentage of these patients, confirmed by positron emission tomography/computer tomography (58).…”

Section: Discussionmentioning

confidence: 95%

“…Looking for new predictive biomarkers, prostate cancer related markers have been evaluated in TNBC for additional treatment options. In this context, based on findings in prostate cancer (PCA), the prostate specific membrane antigen (PSMA) has become an attractive molecular target for oncological imaging and radionuclide therapy using PSMA PET/CT in TNBC (10,11). In addition, among the different subtypes defined (12), the luminal androgen receptor (LAR) subtype was found to be enriched in mRNA expression of androgen receptor (AR) and several downstream AR targets, resulting in enhanced sensitivity to the AR antagonist bicalutamide (13) which qualifies AR as a suitable target in LAR TNBC.…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer

et al. 2020

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Background: We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup. Method: Blood from 41 TNBC pts (n = 41 before / 26 after therapy) was analyzed for CTCs applying the AdnaTest EMT-2/Stem Cell Select. Multimarker RT-qPCR allowed the detection of the prostate specific antigen PSA, the prostate specific membrane antigen PSMA, full-length androgen receptor (AR-FL), and AR splice-variant seven (AR-V7). Results: Before therapy, at least one prostate cancer related gene was detected in 15/41 pts (37%). Notably, in 73% of AR-FL positive cases, AR-V7 was co-expressed. After therapy, CTCs of only one patient harbored prostate cancer related genes. AR-V7+ and PSMA+ CTCs significantly correlated with early relapse (p = 0.041; p = 0.00039) whereas PSMA+ CTCs also associated with a reduced OS (p = 0.0059). This correlation was confirmed for PSMA+ CTCs in univariate (PFS p = 0.002; OS p = 0.015), but not multivariate analysis. Conclusion: Although CTCs that expressed prostate cancer related genes were eliminated by the given therapy, PSMA+ CTCs significantly identified pts at high risk for relapse. Furthermore, AR inhibition, often discussed for this BC subgroup, might not be successful in the primary setting of the disease since we identified AR-FL+ CTCs together with AR-V7+ CTCs, associated with therapeutic failure.

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“…Several case reports or series have shown the potential of PSMA-targeted imaging in breast cancer among which also cases of TNBC [24–26]. A detailed evaluation of the expression on the tumor cells itself and the endothelium of the tumor vessels revealed a higher expression on the endothelium of the tumor vessels, with higher expression rates especially in TNBC in comparison to other breast cancer entities [25, 27]. In this study, we evaluate systematically and show for the first time in vitro and in vivo the potential of targeting of neo-vasculature-associated PSMA by a radiolabeled PSMA-ligand as a promising therapy option in TNBC.…”

Section: Discussionmentioning

confidence: 99%

Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer

et al. 2019

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BackgroundTriple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT).MethodsTube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy. A binding study with 68Ga-labeled PSMA-addressing ligand was used to indicate targeting potential of PSMA on tumor-conditioned HUVEC cells. For mimicking of the therapeutic application, tube formation potential and vitality of tumor-conditioned HUVEC cells were assessed following an incubation with radiolabeled PSMA-addressing ligand [177Lu]-PSMA-617. For in vivo experiments, NUDE mice were xenografted with triple-negative breast cancer cells MDA-MB231 or estrogen receptor expressing breast cancer cells MCF-7. Biodistribution and binding behavior of [68Ga]-PSMA-11 was investigated in both tumor models at 30 min post injection using μPET. PSMA- and CD31-specific staining was conducted to visualize PSMA expression and neovascularization in tumor tissue ex vivo.ResultsThe triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of PSMA was efficiently addressed by radiolabeled PSMA-specific ligands. 177Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. In vivo, as visualized by μPET, radiolabeled PSMA-ligand accumulated specifically in the triple-negative breast cancer xenograft MDA-MB231 (T/B ratio of 43.3 ± 0.9), while no [68Ga]-PSMA-11 was detected in the estrogen-sensitive MCF-7 xenograft (T/B ratio of 1.1 ± 0.1). An ex vivo immunofluorescence analysis confirmed the localization of PSMA on MDA-MB231 xenograft-associated endothelial cells and also on TNBC cells.ConclusionsHere we demonstrate PSMA as promising target for two-compartment endogenous radio-ligand therapy of triple-negative breast cancer.

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Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases

Cited by 64 publications

References 39 publications

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer

Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer

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