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

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Increasing recent experimental evidence supports the hypothesis of small populations of cancer cells within the tumor mass with tumor initiating, stem cell potential. In 2007/2008, CD133 has been identified and discussed as a putative surrogate marker for such cell populations (CSC/TIC) in colorectal tumors. However, the hypothesis that CD133 positive colorectal cancer cell populations impair long-term survival after treatment and could explain the development of secondary tumors leading to the relapse of the disease still needs further studies. The proposed cooperative project was thus designed to achieve the following three major objectives: • Evaluate the therapeutic response and pathophysiologic survival capacity in established CRC models in vitro relative to CD133 expression.• Design and initiate in vivo studies to identify the tumor initiating potential of colorectal tumor cell line subpopulations and obtain CD133+/CD133- cell populations from xenografts.• Isolate CD133+/CD133- cell subpopulations from primary rectal cancers for maintenance in culture, expression profiling and to evaluate their potential relevance for resistance to chemo-radiotherapy.Our strategy to closely collaborate with the DFG-KFO 179 offers the unique ability to extend the necessary basic research set-up towards a state-of-the-art translational and clinically-relevant approach.