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

最近越来越多的实验证据支持肿瘤块内具有肿瘤起始干细胞潜能的小群体癌细胞的假设。在2007/2008年，CD 133已被确定并讨论为结直肠肿瘤中此类细胞群（CSC/TIC）的假定替代标志物。然而，CD 133阳性结直肠癌细胞群损害治疗后的长期生存并可以解释导致疾病复发的继发性肿瘤的发展的假设仍需要进一步研究。因此，拟议的合作项目旨在实现以下三个主要目标：·评估相对于CD 133表达的体外已建立的CRC模型的治疗反应和病理生理存活能力。设计并启动体内研究，以确定结直肠肿瘤细胞系亚群的肿瘤引发潜力，并从异种移植物中获得CD 133 +/CD 133-细胞群。·从原发性直肠癌中分离CD 133 +/CD 133-细胞亚群，用于培养、表达谱分析，并评估其与放化疗抗性的潜在相关性。我们与DFG-KFO 179密切合作的策略提供了独特的能力，可以将必要的基础研究设置扩展到最先进的转化和临床相关方法。

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.