LABORATORY ONCOLOGY
TRANSLATIONAL RESEARCH

We expose cancer’s weak spots

prof. RNDr. Renata Veselská, Ph.D., MSc

Research focus
Laboratory translational research – with the main focus being on pediatric oncology – in close cooperation with clinicians and pathologists represents an important approach to bringing new information concerning tumor biology from bench to bedside. This strategy encompasses especially the identification of activated signaling molecules within tumors that can be targeted by specific low-molecular-weight inhibitors. In ad­dition to this, our research is also aimed at the investigation of cancer stem cell phenotype in relation to the tumorigenicity and resistance to conventional therapy.

Research objectives

  • The identification of activated RTK and downstream signaling pathways as druggable molecular targets in relapsed / refractory pediatric solid tumors and giant cell tumor of the bone.
  • Analysis of the expression of key stemness factors and p53 family proteins in relation to the tumorigeni­city of sarcoma cells.
  • Deciphering the role of mitochondrial dynamics and autophagy in acquisition of stemness using clinica­lly relevant models of resistance development in pediatric solid tumors.

Main partners

  • Children’s Hospital of Philadelphia, PA, USA (Dr. Michael Hogarty)
  • University of Porto, Portugal (Dr. Lucília Saraiva)
  • University of Sydney, Australia (Dr. Patric Jan Jansson)
  • Karolinska Institutet, Stockholm, Sweden / Medical University of Vienna, Austria (Prof. Dr. Igor Adameyko)

Offered services and expertise

  • Primary cultures of human solid tumors.
  • Functional assays on cancer stem cell phenotype (including in vivo tumorigenicity testing).
  • Analyses of activated cell signaling pathways using phosphoprotein arrays.
  • Detailed morphological and gene expression studies on tumor tissue samples, cancer cell lines and xenograft tumors.

Top publications

  • Skoda J, Neradil J, Staniczkova Zambo I, Nunukova A, Macsek P, Borankova K, Dobrotkova V, Nemec P, Sterba J, Veselska R: Serial xenotransplantation in NSG mice promotes a hybrid epithelial/mesenchymal gene expression signature and stemness in rhabdomyosarcoma cells. Cancers 12, Art. No. 196, 2020.
  • Mikulenkova E, Neradil J, Vymazal O, Skoda J, Veselska R: NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation. Cells 9, Art. No. 692, 2020.
  • Veselska R, Jezova M, Kyr M, Mazanek P, Chlapek P, Dobrotkova V, Sterba J: Comparative Analysis of Putative Prognostic and Predictive Markers in Neuroblastomas: High Expression of PBX1 Is Associated with a Poor Response to Induction Therapy. Frontiers in Oncology 9, Art. No. 1221, 2019.
  • Gomes S, Raimundo L, Soares J, Loureiro JB, Leão M, Ramos H, Monteiro MN, Lemos A, Moreira J, Pinto M, Chlapek P, Veselska R, Sousa E, Saraiva L: New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma. Cancer Letters 446, 90-102, 2019.
  • Sramek M, Neradil J, Macigova P, Mudry P, Polaskova K, Slaby O, Noskova H, Sterba J, Veselska R: Effects of sunitinib and other kinase inhibitors on cells harboring a PDGFRB mutation associated with infantile myofibromatosis. International Journal of Molecular Sciences 19, Art. No. 2599, 2018.

Other selected results

Our previous research projects were focused on apoptosis accompanying retinoid-induced differentiation of cancer cells and we also described the mechanisms how to enhance the retinoid-induced cell differentiation of cell lines derived from pediatric solid tumors by inhibitors of lipoxygenases and cyclooxygenases. We also accomplished other studies on the expression of cancer stem cell markers in neurogenic tumors and in sarcomas. The most important results of this research concern the identification of cells displaying CD133/nestin phenotype in pediatric sarcomas, the detailed morphological analyses of the atypical subcellular localization of these two most important CSCs markers – CD133 and nestin – in neurogenic tumors and sarcomas, and  especially the association of the Sox2 expression with tumorigenicity in sarcoma cells.