Therapeutic and Diagnostic Potential of Folic Acid Receptors and Glycosylphosphatidylinositol (GPI) Transamidase in Prostate Cancer

Author:

Hoffmann Marco12,Ermler Thomas Frank12,Hoffmann Felix12,Alexa Radu12,Kranz Jennifer123,Steinke Nathalie24ORCID,Leypold Sophie25,Gaisa Nadine Therese256,Saar Matthias12ORCID

Affiliation:

1. Department of Urology and Pediatric Urology, University Medical Center RWTH Aachen, 52074 Aachen, Germany

2. Center for Integrated Oncology (CIO), University Hospital RWTH Aachen, 52074 Aachen, Germany

3. Department of Urology and Kidney Transplantation, Martin Luther University, 06097 Halle (Saale), Germany

4. Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany

5. Institute of Pathology, University Hospital RWTH Aachen, 52074 Aachen, Germany

6. Institute of Pathology, University Hospital Ulm, 89081 Ulm, Germany

Abstract

Due to the proliferation-induced high demand of cancer cells for folic acid (FA), significant overexpression of folate receptors 1 (FR1) is detected in most cancers. To our knowledge, a detailed characterization of FR1 expression and regulation regarding therapeutic and diagnostic feasibilities in prostate cancer (PCa) has not been described. In the present study, cell cultures, as well as tissue sections, were analyzed using Western blot, qRT-PCR and immunofluorescence. In addition, we utilized FA-functionalized lipoplexes to characterize the potential of FR1-targeted delivery into PCa cells. Interestingly, we detected a high level of FR1-mRNA in healthy prostate epithelial cells and healthy prostate tissue. However, we were able to show that PCa cells in vitro and PCa tissue showed a massively enhanced FR1 membrane localization where the receptor can finally gain its function. We were able to link these changes to the overexpression of GPI–transamidase (GPI-T) by image analysis. PCa cells in vitro and PCa tissue show the strongest overexpression of GPI-T and thereby induce FR1 membrane localization. Finally, we utilized FA-functionalized lipoplexes to selectively transfer pDNA into PCa cells and demonstrate the therapeutic potential of FR1. Thus, FR1 represents a very promising candidate for targeted therapeutic transfer pathways in PCa and in combination with GPI-T, may provide predictive imaging in addition to established diagnostics.

Funder

Faculty of Medicine RWTH Aachen University

Publisher

MDPI AG

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