Die Expression des prostataspezifischen Membranantigens (PSMA) beim Mammakarzinom

Zusammenfassung

Hintergrund Das prostataspezifische Membranantigen (PSMA) ist für Mammakarzinompatientinnen ein vielversprechendes Protein. Es wurde bisher nicht nur beim Prostatakarzinom nachgewiesen, sondern wird auch von den Tumor- sowie Endothelzellen der Tumorgefäße des Mammakarzinoms exprimiert. Das PSMA hat eine Rolle bei der Tumorprogression und Neubildung von Gefäßen. Deshalb wurden bereits viele PSMA-gerichtete diagnostische und therapeutische Verfahren entwickelt.

Methode Diese Arbeit ist eine allgemeine und gegliederte Übersicht über das PSMA und dessen onkogenetisches Potenzial, mit dem Fokus auf dessen Rolle beim Mammakarzinom. Für dieses narrative Review wurde eine selektive Literaturrecherche via PubMed und der Bibliothek des Universitätsklinikums Freiburg angefertigt. Hierbei wurden folgende Schlüsselwörter verwendet: „PSMA“, „PSMA and breast cancer“, „PSMA PET/CT“, „PSMA tumor progression“. Relevante Artikel wurden explizit durchgelesen, bearbeitet und zusammengefasst.

Schlussfolgerung Das PSMA könnte, insbesondere beim triple-negativen Mammakarzinom, eine neue diagnostische und therapeutische Alternative darstellen. Es scheint ein möglicher prädiktiver und prognostischer Marker zu sein.

Abstract

Background Prostate specific membrane antigen (PSMA) is a promising protein for breast cancer patients. It has not only been detected in prostate cancer but is also expressed by tumor cells and the endothelial cells of tumor vessels in breast cancer patients. PSMA plays a role in tumor progression and tumor angiogenesis. For this reason, a number of diagnostic and therapeutic methods to target PSMA have been developed.

Method This paper provides a general structured overview of PSMA and its oncogenic potential, with a special focus on its role in breast cancer. This narrative review is based on a selective literature search carried out in PubMed and the library of Freiburg University Clinical Center. The following key words were used for the search: “PSMA”, “PSMA and breast cancer”, “PSMA PET/CT”, “PSMA tumor progression”. Relevant articles were explicitly read through, processed, and summarized.

Conclusion PSMA could be a new diagnostic and therapeutic alternative, particularly for triple-negative breast cancer. It appears to be a potential predictive and prognostic marker.

Schlüsselwörter

PSMA - Mammakarzinom - Radioligandentherapie - Immunhistochemie - PET/CT

Keywords

PSMA - breast cancer - radioligand therapy - immunohistochemistry - PET/CT

• Literatur

• 1 OʼKeefe DS, Bacich DJ, Heston WDW. Prostate Cancer: Biology, Genetics and the new Therapeutics. Totowa: Humana Press; 2001.
• 2 Bacich DJ, Pinto JT, Tong WP. et al. Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. Mamm Genome 2001; 12: 117-123
• 3 OʼKeefe DS, Su SL, Bacich DJ. et al. Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. Biochim Biophys Acta 1998; 1443: 113-127
• 4 Horoszewicz JS, Leong SS, Chu TM. et al. The LNCaP cell line-a new model for studies on human prostatic carcinoma. Prog Clin Biol Res 1980; 37: 115-132
• 5 Devlin AM, Ling E, Peerson JM. et al. Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. Hum Mol Genet 2000; 9: 2837-2844
• 6 Carter RE, Feldman AR, Coyle JT. et al. Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc Natl Acad Sci 1996; 93: 749-753
• 7 Stauch Slusher B, Tsai G, Yoo G. et al. Immunocytochemical localization of the N-acetyl-aspartyl-glutamate (NAAG) hydrolyzing enzyme N-acetylated α-linked acidic dipeptidase (NAALADase). J Comp Neurol 1992; 315: 217-229
• 8 Mesters JR, Barinka C, Li W. Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer. EMBO J 2006; 25: 1375-1384
• 9 Rajasekaran AK, Anilkumar G, Christiansen JJ. Is prostate-specific membrane antigen a multifunctional protein?. Am J Physiol Cell Physiol 2005; 288: 975-981
• 10 Minner S, Wittmer C, Graefen M. et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 2011; 71: 281-288
• 11 Kinoshita Y, Kuratsukuri K, Landas S. et al. Expression of Prostate-Specific membrane antigen in normal and malignant human tissues. World J Surg 2006; 30: 628-636
• 12 Silver DA, Pellicer I, Fair WR. et al. Prostate-Specific Membrane Antigen Expression in Normal and Malignant Human Tissues. Clin Cancer Res 1997; 3: 81-85
• 13 Wright GL, Haley C, Beckett M. et al. Expression of Prostate-Specific Membrane Antigen in normal, benign, and malignant prostate tissues. Urol Oncol Semin Orig Investig 1995; 1: 18-28
• 14 Wang H, Wang L, Song W. et al. Expression of Prostate-Specific Membrane Antigen in Lung Cancer Cells and Tumor Neovasculature Endothelial Cells and Its Clinical Significance. PLoS One 2015;
• 15 Chang SS, Reuter VE, Heston WD. et al. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res 1999; 59: 3192-3198
• 16 Kasoha M, Unger C, Solomayer E. et al. Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clin Exp Metastasis 2017; 34: 479-490
• 17 Tolkach Y, Gevensleben H, Bundschuh R. et al. Prostate‑specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy. Breast Cancer Res Treat 2018; 169: 447-455
• 18 Wernicke AG, Varma S, Greenwood EA. et al. Prostate-specificmembrane antigen expression in tumor-associated vasculature of breast cancers. Apmis 2014; 122: 482-489
• 19 Ross JS, Schenkein D, Webb I. et al. Expression of prostate specific membrane antigen in the neo-vasculature of non-prostate cancers. J Clin Oncol 2004; 22: 3110
• 20 Mhawech-Fauceglia P, Zhang S, Terracciano L. et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: An immunohistochemical study using mutiple tumour tissue microarray technique. Histopathology 2007; 50: 472-483
• 21 Nomura N, Pastorino S, Jiang P. et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 2004; 14: 26
• 22 Pinto JT, Suffoletto BP, Berzin TM. et al. Prostate-specific Membrane Antigen: A Novel Folate Hydrolase in Human Prostatic Carcinoma Cells. Clin Cancer Res 1996; 2: 1445-1451
• 23 Yao V, Berkman CE, Choi JK. et al. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. Prostate 2010; 70: 305-316
• 24 Löffler G, Petrides PE, Heinrich PC. Löffler/Petrides Biochemie und Pathobiochemie. 8. Aufl.. Berlin: Springer; 2007.
• 25 Gordon IO, Tretiakova MR, Noffsinger AE. et al. Prostate-specific membrane antigen expression in regeneration and repair. Mod Pathol 2008; 21: 1421-1427
• 26 Bradbury R, Jiang WENG, Cui Y. MDM2 and PSMA Play Inhibitory Roles in Metastatic Breast Cancer Cells Through Regulation of Matrix Metalloproteinases. Anticancer Res 2016; 36: 1143-1151
• 27 Oliner J, Pietenpol J, Thiagalingam S. et al. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 1993; 362: 857-860
• 28 Caromile LA, Shapiro LH. PSMA redirects MAPK to PI3K‑AKT signaling to promote prostate cancer progression. Mol Cell Oncol 2017; 4: 1-3
• 29 Liu H, Rajasekaran AK, Moy P. et al. Constitutive and Antibody-induced Internalization of Prostate-specific Membrane Antigen. Cancer Res 1998; 8: 4055-4060
• 30 Nguyen DP, Xiong PL, Liu H. et al. Induction of PSMA and Internalization of an Anti-PSMA mAb in the Vascular Compartment. Mol Cancer Res 2016; 14: 1045-1053
• 31 Conway RE, Petrovic N, Zhong L. et al. Prostate-Specific Membrane Antigen Regulates Angiogenesis by Modulating Integrin Signal Transduction. Mol Cell Biol 2006; 26: 5310-5324
• 32 Morgenroth A, Tinkir E, Vogg ATJ. et al. Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer. Breast Cancer Res 2019; 21: 116
• 33 Liu T, Jabbes M, Nedrow-Byers JR. et al. Detection of prostate-specific membrane antigen on HUVECs in response to breast tumor-conditioned medium. Int J Oncol 2011; 38: 1349-1355
• 34 Leitlinienprogramm Onkologie. Interdisziplinäre S3-Leitlinie für die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms 2018. https://www.leitlinienprogrammonkologie.de/leitlinien/mammakarzinom/
• 35 Zidan J, Dashkovsky I, Stayerman C. et al. Comparison of HER‑2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 2005; 93: 552-556
• 36 Alhuseinalkhudhur A, Lubberink M, Lindman H. et al. Kinetic analysis of HER2-binding ABY‑025 Affibody molecule using dynamic PET in patients with metastatic breast cancer. EJNMMI Res 2020; 10: 21
• 37 Bertagna F, Albano D, Cerudelli E. et al. Radiolabelled PSMA PET/CT in breast cancer. A systematic review. Nucl Med Rev Cent East Eur 2020; 23: 32-35
• 38 Passah A, Arora S, Damle N. et al. 68Ga-Prostate-Specific Membrane Antigen PET/CT in Triple-Negative Breast Cancer. Clin Nucl Med 2018; 43: 460-461
• 39 Sathekge M, Modiselle M, Vorster M. et al. 68Ga-PSMA imaging of metastatic breast cancer. Eur J Nucl Med Mol Imaging 2015; 42: 1482-1483
• 40 Sathekge M, Lengaga T, Modiselle M. et al. 68Ga-PSMA-HBED‑CC PET imaging in breast carcinoma patients. Eur J Nucl Med Mol Imaging 2017; 44: 689-694
• 41 Medina-Ornelas S, García-Perez F, Estrada-Lobato E. et al. 68Ga-PSMA PET/CT in the evaluation of locally advanced and metastatic breast cancer, a single center experience. Am J Nucl Med Mol Imaging 2020; 10: 135-142
• 42 Kasimir-Bauer S, Keup C, Hoffman O. et al. Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer. Front Oncol 2020; 10: 1-12
• 43 Aktas B, Kasimir-Bauer S, Müller V. et al. Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC Cancer 2016; 16: 1-8
• 44 Onstenk W, Sieuwerts AM, Mostert B. et al. Molecular characteristics of circulating tumor cells resemble the liver metastasis more closely than the primary tumor in metastatic colorectal cancer. Oncotarget 2016; 7: 59058-59069
• 45 Lianidou E, Pantel K. Liquid biopsies. Genes, Chromosomes and Cancer 2019; 58: 219-232
• 46 Yadav MP, Ballal S, Bal C. et al. Efficacy and Safety of 177Lu-PSMA‑617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients. Clin Nucl Med 2020; 45: 19-31
• 47 Rahbar K, Ahmadzaehfar H, Kratochwil C. et al. German Multicenter Study Investigating 177Lu-PSMA‑617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med 2017; 58: 85-90
• 48 Violet J, Sandhu A, Iravani A. et al. Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA‑617 Theranostics in Metastatic Castration-Resistant Prostate Cancer. J Nucl Med 2020; 61: 857-865
• 49 Current K, Meyer C, Magyar C. et al. Investigating PSMA-Targeted Radioligand Therapy Efficacy as a Function of Cellular PSMA Levels and Intratumoral PSMA Heterogeneity. Clin Cancer Res 2020; 26: 2946-2955
• 50 Flores O, Santra S, Kaittanis C. et al. PSMA-targeted theranostic nanocarrier for prostate cancer. 2017; 7: 2477-2494
• 51 Maurer T, Graefen M, van der Poel H. et al. Prostate-Specific Membrane Antigen – Guided Surgery. J Nuclear Med 2020; 61: 6-13
• 52 Rauscher I, Düwel C, Wirtz M. et al. Value of 111 In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up. BJU Int 2017; 120: 40-47
• 53 Von Hoff D, Mita MM, Ramanathan RK. et al. Phase I Study of PSMA-Targeted Docetaxel-Containing Nanoparticle BIND‑014 in Patients with Advanced Solid Tumors. Clin Cancer Res 2016; 22: 3157-3164