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NCT Junior Research Group Prostate Cancer Biomarkers

Prostate cancer (PCa) is one of the most frequent malignancies in men. However, currently used tumor markers for early diagnosis are lacking specificity and sensitivity. In addition, progression and treatment response are still not sufficiently predictable. Due to its molecular heterogeneity, PCa represents an ideal candidate for exploring and developing a personalized medicine approach.

In this project, liquid biopsies (blood, urine) from patients with suspected or diagnosed PCa at different disease stages will be collected and used to identify and validate biomarkers with diagnostic, prognostic and predictive potential. Furthermore, these biomarkers will be characterized in detail in order to determine their functional role in PCa onset, progression and metastasis as well as therapy resistance. Overall, the focus of the junior research group lies on translational uro-oncology and the establishment of molecular markers with higher clinical performance helping to refine early diagnosis as well as individual risk stratification and treatment planning for PCa patients.

Long-term objectives

The long-term objectives of the project are:

  • development of non- or minimal-invasive diagnostic tools to avoid unnecessary prostate biopsies
  • implementation of prognostic and predictive factors in treatment decisions and thus prevention of ineffective therapies
  • shedding light on mechanisms of tumor onset, progression and metastasis as well as therapy resistance
  • establishing strategies to circumvent therapy resistance
  • identification of novel therapeutic targets
Prostate Cancer Biomarkers

The microRNAs miR-26a and miR-138 are potential biomarker candidates with known anti-tumor and chemosensitizing activities. Both microRNAs are down-regulated in PCa (Erdmann et al. 2014).

(A) The microRNAs miR-26a and miR-138 exert anti-proliferative effects in PCa cells by blocking the G1/S-phase transition via a concerted inhibition of crucial cell cycle regulators (Erdmann et al. 2016). (B) For example, transfection of PC3 PCa cells with the respective microRNA mimics diminished the protein level of the target CDK6. Control treatment: miR-CON; reference protein: α-tubulin. (C) CDK6 is highly expressed in PCa tissues in comparison to non-malignant prostate tissues as evidenced by immunohistochemical staining on tissue microarrays (brown: CDK6 protein, blue: nuclei).
Copyright: Kati Erdmann

Methodology

  • collection and processing of urine and blood samples from patients with suspected or diagnosed PCa as well as from control patients, documentation of clinico-pathological and follow-up data
  • culture of human tumor cell lines and non-malignant cells
  • isolation of exosomes, nucleic acids and proteins from urine, blood and cell samples
  • transient transfection of tumor cells: modulation of gene and microRNA expression
  • chemo- and radiosensitization of tumor cells
  • transfer of exosomes from chemo- and radioresistant cell lines and from patients receiving systemic therapy to sensitive cells
  • assays for the characterization of cell growth (proliferation, viability, apoptosis, cell cycle, cell colony formation, wound healing, migration, invasion)
  • quantitative PCR for quantitation of gene expression
  • gel electrophoresis
  • cloning, sequencing, reporter gene assays
  • protein analysis (Western Blot, Slot Blot, ELISA)
  • immunohistochemistry and in situ-hybridization of tissue microarrays
  • microscopy
  • statistical assessment of diagnostic, prognostic and predictive value of selected biomarkers

Team

Dr. Kati Erdmann
Junior Group Leader
Phone: +49 (0)351 458 5683
E-Mail: kati.erdmann(at)uniklinikum-dresden.de

Lukas Donix
PhD Student
Phone: +49 (0)351 458 5683
E-Mail: lukas.donix(at)uniklinikum-dresden.de

Ulrike Lotzkat
Technical Assistant
Phone: +49 (0)351 458 4544
Email: ulrike.lotzkat(at)uniklinikum-dresden.de

 

2018

Fuessel S, Lohse-Fischer A, Vu Van D, Salomo K, Erdmann K, Wirth MP (2018). Quantification of MicroRNAs in Urine-Derived Specimens. In Schulz WA et al. (eds.): Urothelial Carcinoma: Methods and Protocols, Methods in Molecular Biology, vol. 1655: 201-226, ©Springer Science+Business Media LLC 2017

2017

Erdmann K* & Kaulke K*, Rieger C, Wirth MP, Fuessel S (2017). Induction of alpha‑methylacyl‑CoA racemase by miR‑138 via up‑regulation of β‑catenin in prostate cancer cells. J Cancer Res Clin Oncol 143(11):2201-2210 *Co-first authors

Erdmann K* & Ringel J*, Hampel S, Wirth MP, Fuessel S (2017). Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation. Beilstein J Nanotechnol 8:1307-1317 *Co-first authors

Kaufmann A, Hampel S, Rieger C, Kunhardt D, Schendel D, Füssel S, Schwenzer B, Erdmann K (2017). Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes. J Nanobiotechnology 15(1):53

2016

Erdmann K* & Kaulke K*, Rieger C, Salomo K, Wirth MP, Fuessel S (2016). MiR-26a and miR-138 block the G1/S transition by targeting the cell cycle regulating network in prostate cancer cells. J Cancer Res Clin Oncol 142(11):2249-61 *Co-first authors

2015

Castro Nava A, Cojoc M, Peitzsch C, Cirillo G, Kurth I, Fuessel S, Erdmann K, Kunhardt D, Vittorio O, Hampel S, Dubrovska A (2015). Development of novel radio-chemotherapy approaches targeting prostate tumor progenitor cells using nanohybrids. Int J Cancer 137(10):2492-2503

Cojoc M, Peitzsch C, Kurth I, Trautmann F, Kunz-Schughart LA, Telegeev GD, Stakhovsky EA, Walker JR, Simin K, Lyle S, Fuessel S, Erdmann K, Wirth MP, Krause MP, Baumann M, Dubrovska A (2015). Expression of stem cell marker aldehyde dehydrogenase is regulated by β-catenin/TCF and promotes radioresistance in prostate cancer progenitor cells. Cancer Res 75(7):1482-1494

Toma M, Wehner R, Kloß A, Hübner L, Fodelianaki G, Erdmann K, Füssel S, Zastrow S, Meinhardt M, Seliger B, Brech D, Noessner E, Tonn T, Schäkel K, Bornhäuser M, Bachmann M, Wirth MP, Baretton GB, Schmitz M (2015). Accumulation of tolerogenic 6-sulfo LacNAc+ dendritic cells in renal cell carcinoma is associated with poor prognosis. OncoImmunology 4(6):e1008342

Rieger C, Kunhardt D, Kaufmann A, Schendel D, Huebner D, Erdmann K, Propping S, Wirth MP, Schwenzer B, Fuessel S, Hampel S (2015). Characterization of different carbon nanotubes for the development of a mucoadhesive drug delivery system for intravesical treatment of bladder cancer. Int J Pharm 479(2):357