Distribution, characteristics and therapeutic relevance of CD133 expressing tumor (stem) cell populations in rectal carcinoma models

• Applicants: Privatdozent Dr. Marian Grade; Professorin Dr. Leoni Kunz-Schughart
• Subject Area: General and Visceral Surgery
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 120038946

• Final Report Year: 2012

Final Report Abstract

The project has gained important insights into a highly relevant topic in cancer research and treatment, the cancer stem cell hypothesis and phenotype in colorectal cancers and the role as well as plasticity of various biomarkers, in particular CD133 and CD44, in CRC cells. Numerous complex and sophisticated in vitro and in vivo experiments were performed. Scientifically, it has been a very challenging and successful project which should be extended to better understand the regulation of putative cancer stem cell markers in pathophysiological tumor environments and to unravel the level and potential of cancer cell phenotype switching, i.e. the switch between cancer stemness and non-stemness. However, we could not identify and isolate a clear therapeutically relevant phenotype by the markers studied so far. We intend to come up with a new concept using the scientific findings and technical expertise to focus on a more specific therapy-relevant aspect related to cancer cell phenotype. This concept will clearly be based on our newest finding that cell subpopulations isolated from a cell line xenograft may differ in their tumor take rate in contrast to the cell line subpopulations discriminated in vitro by the same biomarkers.

Publications

• Challenges to identify CD133 expression in cancer cells. 19th Annual Conference of the German Society for Cytometry (DGfZ), Leipzig, Germany, 14.-16.10.2009
  Dittfeld C., Peickert S., Kunz-Schughart L.A.
  
• In vitro radio- and chemosensitivity of CD133+/- subpopulations from two CRC cell lines.1st International Meeting on Molecular-Based Treatment of GI-Cancer, Göttingen, Germany, 23.–24.09.2009
  Peickert S., Dittfeld C., Dietrich A., Garbe Y., Grade M., Ried Th., Kunz-Schughart L.A.
  
• Is CD133 expression in colorectal cancer lines selective for a tumor-initiating or radioresistant cell population? 55th Annual Meeting of the Radiation Research Society, Savannah, USA, 3.-7.10.2009
  Dittfeld C., Dietrich A., Peickert S., Grade M., Ried Th., Kunz-Schughart L.A.
  
• Response of CD133+/- subpopulations of CRC cell lines to radio- and chemotherapy. Joint ECCO 15 - 34th ESMO Multidisciplinary Congress, Berlin, Germany, 20.-24.09.2009
  Dittfeld C., Peickert S., Dietrich A., Grade M., Ried Th., Kunz-Schughart L.A.
  
• Stem Cells, Cancer Stem Cells, Cancer, Cancer Tissue: Where is the link? 19th Annual Conference of the German Society for Cytometry (DGfZ), Leipzig, Germany, 14.-16.10.2009
  Kunz-Schughart L.A.
  
• The ambiguous behavior of CD133+/- subpopulations from different colorectal cancer cell lines. 19th Annual Conference of the German Society for Cytometry (DGfZ), Leipzig, Germany, 14.-16.10.2009
  Peickert S., Dittfeld C., Dietrich A., Garbe Y., Grade M., Ried Th., L.A. Kunz-Schughart
  
• A story of complexity and discrepancy: CD133 expression and tumorigenicity of colon cancer cell line subpopulations. EACR21, 21st Meeting of the European Association for Cancer Research, Oslo, Norway, 26.-29.06.2010
  Garbe Y., Dittfeld C., Peickert S., Waurig J., Dietrich A., Grade M., Ried T., Kunz-Schughart L.A.
  
• CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC line HCT-116. Radiother. Oncol. 94(3):375-83 (2010)
  Dittfeld C., Dietrich A., Peickert S., Hering S., Baumann M., Grade M., Ried T., Kunz- Schughart L.A.
  
• Hunting for the Cancer Stem Cell in solid tumors and established cell lines. 12th International Tumor Microenvironment Workshop, Toronto, Canada. 02.-05.05.2010
  Dittfeld C., Garbe Y., Waurig J.. Peickert S., Kunz-Schughart L.A.
  
• Impact of the pathophysiological milieu on the survival of CD133+ and CD133- colorectal tumor cell populations. 19th Symposium. Experimentelle Strahlentherapie und Klinische Strahlenbiologie. Dresden, Germany, 04.–06.03.2010
  Waurig J., Peickert S., Dittfeld C., Huether M., Garbe Y., Kunz-Schughart L. A.
  
• Impact of various milieu conditions on the survival of CD133+ and CD133-/low colorectal tumor cell populations. ESTRO29, 29th Annual Meeting of the European Society for Therapeutic Radiology and Oncology, Barcelona, 12.-16.09.2010
  Waurig J., Peickert S., Dittfeld C., Garbe Y., Kunz-Schughart L. A.
  
• A brief introduction to navigate through the foggy sea of cancer stem cell research. 20th Annual Conference of the German Society for Cytometry (DGfZ), Bonn, Germany, 10.-12.10.2011
  Kunz-Schughart L.A.
  
• CD133-/low HT29 cells rapidly reexpress CD133 in vitro and in vivo and show enhanced survival under physiological oxygen conditions. The European Multidisciplinary Cancer Congress (ECCO), Stockholm, Sweden, 23.-27.09.2011
  Waurig J., Dittfeld C., Garbe Y., Peickert S., Dietrich A.
  
• Genome and transcriptome profiles of CD133-positive colorectal cancer cells. Am. J. Pathol. 178:1478-88 (2011)
  Gaiser T., Camps J., Meinhardt S., Wangsa D., Nguyen Q.T.,Varma S., Dittfeld C., Kunz-Schughart L.A., Kemmerling R., Becker M.R., Heselmeyer-Haddad K., Ried T.
  
• Impact of long-term acidosis on the expression pattern of putative cancer stem cell biomarkers in colorectal cancer cell lines, 20th Annual Conference of the German Society for Cytometry (DGfZ), Bonn, Germany, 10.-12.10.2011
  Große-Gehling P., Mamat C., Kunz-Schughart L.A.
  
• Status and plasticity of CD133 and CD44 expression in three colorectal cancer cell lines. 20th Annual Conference of the German Society for Cytometry (DGfZ), Bonn, Germany, 10.-12.10.2011
  Lydia Kabus, Yvette Garbe, Marit Wondrak, Leoni A. Kunz-Schughart
  
• Tumorigenicity of colorectal cancer cell lines with distinct CD133 and CD44 antigen pattern. 20th Annual Conference of the German Society for Cytometry (DGfZ), Bonn, Germany, 10.-12.10.2011
  Waurig J., Kabus L., Dittfeld C., Garbe Y., Wondrak M., Kunz-Schughart L.A.
  
• Cancer stem cells as a predictive factor in radiotherapy. Semin Radiat Oncol. 22(2):151-74 (2012)
  Brunner T.B., Kunz-Schughart L.A., Grosse-Gehling P., Baumann M.
  (See online at https://doi.org/10.1016/j.semradonc.2011.12.003)
• CD133 as a biomarker for putative cancer stem cells in solid tumors: limitations, problems and challenges. J. Pathol. 2012 Aug 16. [Epub ahead of print]
  Grosse-Gehling P., Fargeas C.A., Dittfeld C., Garbe Y., Alison M.R. Corbeil D., Kunz- Schughart L.A.
  (See online at https://doi.org/10.1002/path.4086)
• Redistribution of CD133 and CD44 cell surface presentation in SW620 colorectal cancer cell line xenografts , Cyto 2012, XXVII Annual Congress of the International Society for Advancement of Cytometry, Leipzig, 23.-27.06.2012
  Grosse-Gehling P., Kabus L., Dittfeld C., Waurig J., Kunz-Schughart L.A.