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’Tumor, Stem cells and Tumor Stem Cells’ Barbara Wollenberg

’Tumor, Stem cells and Tumor Stem Cells’ Barbara Wollenberg. Universitätsklinikum Schleswig-Holstein, Campus Lübeck Germany. Stochastic Model. Hierarchic Model. Differentiated Tumor cell. Tumor Precursor cell. Tumor-initiating cell. UK-SH - ENT Lübeck. Theories of Tumor Development.

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’Tumor, Stem cells and Tumor Stem Cells’ Barbara Wollenberg

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  1. ’Tumor, Stem cells and Tumor Stem Cells’ Barbara Wollenberg Universitätsklinikum Schleswig-Holstein, Campus Lübeck Germany

  2. Stochastic Model Hierarchic Model Differentiated Tumor cell Tumor Precursor cell Tumor-initiating cell UK-SH - ENT Lübeck Theories of Tumor Development • Stochastic Model • Hierarchic Model (Tumor stem cell-Hypothesis)

  3. Cancer cells die Chemo- radio- therapy Cancer stem cells survive New Cancer arises from cancer stem cells UK-SH - ENT Lübeck The key to chemo-radioresistence and recurrence ?! … but how to identify tumor stem cells ?

  4. Fusion Stem cell Tumor cell CD34+ Progenitor Prince et.al 2007 ??? Vascular endothelium Immuno-Suppression Inflammation Young et al.2007 Wollenberg et al. 2007 Stem cells and Tumor: Tumorprogression and Metastases CD44+Lin- Tumor stem cell Diffentiation Self-Renewal www.regmed.uni-luebeck.de

  5. UK-SH - ENT Lübeck Many open questions concerning stem cell functions...… ? Attraction/homing ? Characterisation of the niche milieu Formation of new vessels ? Influence on the immune system ? ? Formation of metastases

  6. UK-SH - ENT Lübeck Potential Markers for ‚Tumor-Stem cells‘

  7. UK-SH - ENT Lübeck Potential Markers for ‚Tumor-Stem cells‘

  8. UK-SH - ENT Lübeck Identification of potential tumor stem cells in HNSCC Great individual Heterogeneity !

  9. UK-SH - ENT Lübeck Expressions-ProfilingHNSCC Metastases and Recurrences

  10. UK-SH - ENT Lübeck Chemo- and radioresistence of CD44+lin- cells increased chemoresistence and radioresistance (not shown) of permanent cell lines derived from metastases versus primary tumor

  11. UK-SH - ENT Lübeck Reconsideration of tumor therapeutics ?! • Individual tumor profiling • Individualized tumor stem cell therapeutics • Targeting der ‚multidrug resistance‘ Mechanisms • Targeting der DNA-Repair-Mechanisms • Blocking of self renewal cascades (WNT,BMP Signaling) • Acceleration of differentiation • Blocking of homing (e.g.CXCR4) • characterisation of the stem cell niche • ‚Tumor-Stem cells‘ as target for innovative Vaccine strategies

  12. Faces behind the projects

  13. Stammzellen und Tumor: Tumorprogression und Metastasierung In Vivo Imaging Migration und Homing von Stammzellen Ausbildung der Stammzellnische Qualität der Stammzelle : Chemoresistenz erhöht Strahlensensitivität erniedrigt Innovationsfond Schleswig Holstein

  14. Rades radio und chemo resitance sens der CD44 vs dem Rest ????

  15. HNSCC DC UK-SH - ENT Lübeck Immunsuppression durch CD34+ Progenitorzellen IFNγ IL-12 Stimulation of Angiogenesis and Metastasis Formation MP Immune Cell Suppression NK Treg IL- 8 T IL-10 B IL-4 Growth factors PGE2 TGF-β IL- 8 IL- 6 IL-10 GM-CSF TGF-β VEGF IL-1 CD34 Immune Cell Alteration and Induction of Cytokine Secretion Mobilization and Attraction of CD34+ Progenitor Cells

  16. UK-SH - ENT Lübeck CD34+ Zellen infiltrieren solide HNSCC … … und sind an der Biosynthese des HNSCC Mikroenvironments beteiligt!

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