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

直肠癌模型中表达 CD133 的肿瘤（干）细胞群的分布、特征和治疗相关性

• 批准号: 120038946
• 负责人: Privatdozent Dr. Marian Grade
• 金额: --
• 依托单位: Klinik und Poliklinik für Strahlentherapie und Radioonkologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/120038946?language=en
• 关键词: Distribution; characteristics; therapeutic; relevance; CD133

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.

最近越来越多的实验证据支持肿瘤肿块内少量癌细胞具有肿瘤启动干细胞潜力的假设。在2007/2008年，CD133已被确定并讨论作为结肠直肠肿瘤中此类细胞群（CSC/TIC）的推定替代标记物。然而，CD133阳性结直肠癌细胞群影响治疗后的长期生存，并可能解释继发性肿瘤的发展导致疾病复发的假设仍需要进一步的研究。因此，拟议的合作项目旨在实现以下三个主要目标：•评估与CD133表达相关的体外CRC模型的治疗反应和病理生理生存能力。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启动潜力，并从异种移植物中获得CD133+/CD133-细胞群。•从原发性直肠癌中分离CD133+/CD133-细胞亚群，维持培养、表达谱，并评估其与化疗放疗耐药性的潜在相关性。我们与DFG-KFO 179密切合作的战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。