Aarhus University Seal

In Prostate Cancer Cells Cytokines Are Early Responders to Gravitational Changes Occurring in Parabolic Flights

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Herbert Schulz, Otto von Guericke University Magdeburg
  • ,
  • Dorothea Dietrichs, Otto von Guericke University Magdeburg
  • ,
  • Markus Wehland
  • Thomas J Corydon
  • Ruth Hemmersbach, Institute for Aerospace Medicine Cologne
  • ,
  • Christian Liemersdorf, Institute for Aerospace Medicine Cologne
  • ,
  • Daniela Melnik, Otto von Guericke University Magdeburg
  • ,
  • Norbert Hübner, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Charité – Universitätsmedizin Berlin
  • ,
  • Kathrin Saar, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association
  • ,
  • Manfred Infanger, Otto von Guericke University Magdeburg
  • ,
  • Daniela Grimm

The high mortality in men with metastatic prostate cancer (PC) establishes the need for diagnostic optimization by new biomarkers. Mindful of the effect of real microgravity on metabolic pathways of carcinogenesis, we attended a parabolic flight (PF) mission to perform an experiment with the PC cell line PC-3, and submitted the resulting RNA to next generation sequencing (NGS) and quantitative real-time PCR (qPCR). After the first parabola, alterations of the F-actin cytoskeleton-like stress fibers and pseudopodia are visible. Moreover, numerous significant transcriptional changes are evident. We were able to identify a network of relevant PC cytokines and chemokines showing differential expression due to gravitational changes, particularly during the early flight phases. Together with differentially expressed regulatory lncRNAs and micro RNAs, we present a portfolio of 298 potential biomarkers. Via qPCR we identified IL6 and PIK3CB to be sensitive to vibration effects and hypergravity, respectively. Per NGS we detected five upregulated cytokines (CCL2, CXCL1, IL6, CXCL2, CCL20), one zink finger protein (TNFAIP3) and one glycoprotein (ICAM1) related to c-REL signaling and thus relevant for carcinogenesis as well as inflammatory aspects. We found regulated miR-221 and the co-localized lncRNA MIR222HG induced by PF maneuvers. miR-221 is related to the PC-3 growth rate and MIR222HG is a known risk factor for glioma susceptibility. These findings in real microgravity may further improve our understanding of PC and contribute to the development of new diagnostic tools.

Original languageEnglish
Article number7876
JournalInternational Journal of Molecular Sciences
Volume23
Issue14
Number of pages17
ISSN1661-6596
DOIs
Publication statusPublished - Jul 2022

    Research areas

  • Carcinogenesis, Cytokines/genetics, Humans, Interleukin-6, Male, MicroRNAs/genetics, Prostatic Neoplasms/genetics, Space Flight, Weightlessness, hypergravity, CARCINOMA CELLS, non-coding, NORMAL THYROID-CELLS, PATTERNS, OVEREXPRESSION, parabolic flight, qPCR, cytokines, RNA sequencing, microgravity, INDUCED APOPTOSIS, prostate cancer, ALTERED GRAVITY, SIMULATED MICROGRAVITY, EXTRACELLULAR-MATRIX, DIFFERENTIATION, PC-3, EXPRESSION

See relations at Aarhus University Citationformats

ID: 276846519