Characterization of CD 26+CD110+ (liver) and CD26+CDCP1+ (lung) cancer stem cell populations, determination of their mutational heterogeneity and the differences of the liver vs. lung niche

结直肠癌是男性和女性中第二常见的癌症。在诊断时，25%的患者确实有转移性疾病，50%的患者在疾病过程中会发生转移性疾病。这种高转移率导致大多数患者最初不适合根治性切除(1)。此外，器官特异性转移确实直接影响这些患者的总体生存。肝转移是最重要的预后指标之一。切除肿瘤可以显著提高患者的存活率。此外，最近的数据显示，在存在无法切除的肺转移的情况下，所有肝转移都被切除的患者的存活率有所提高。然而，与仅有结直肠癌肺转移的患者相比，有结直肠癌肝转移的患者的预后确实要差得多。由此可见，结直肠癌肝、肺转移的肿瘤生物学特性存在差异。在结直肠癌中，一个重要的细胞亚群是肿瘤干细胞(CSC)的转移，它决定了结直肠癌的生物学行为和侵袭性。肿瘤干细胞可以通过它们的表位来检测，因此也可以在转移的情况下被识别。目前，还没有对肿瘤干细胞与器官特异性转移相关的进一步分析，因此，结直肠癌肝和肺转移侵袭性差异的原因尚不清楚。本项目的目的是鉴定CD26+CD110+(肝脏)和CD26+CDCP1+(肺癌)肿瘤干细胞群体，确定它们的突变异质性以及肝和肺生态位的差异。

Colorectal cancer is the second most frequent cancer in men and women. At time of diagnosis 25% of patients do have metastatic disease and 50% of patients will develop metastases during the course of their disease. This high metastatic rate leads to the majority of patients initially not being candidates for curative resection (1). Further, organspecific metastases do directly impact on overall survival in these patients. Liver metastasis is one of the most important prognosticators. Their resection can significantly improve their survival. Adding to this, recent data has shown a survival benefit for patients in whom all liver metastases are resected in the presence of unresectable lung metastases (2). However, patients with colorectal liver metastases do have a considerably worse prognosis compared to patients with colorectal lung metastases alone (3). Therefore, this suggests that there are differences in tumor biology of colorectal liver and lung metastases. An important subpopulation of cells in colorectal cancer are cancer stem cells (CSC) metastasis that confer the biological behavior and aggressiveness of the colorectal cancer. Cancer stem cells can be detected by their epitopes and thus also be identified in case of metastasis. Today, no further analysis of cancer stem cells concerning organspecific metastasis has been performed and consequently the reason for the differences in aggressiveness of colorectal liver and lung metastases remains unclear. The aim of this project is the characterization of CD 26+CD110+ (liver) and CD26+CDCP1+ (lung) cancer stem cell populations, determination of their mutational heterogeneity and the differences of the liver vs. lung niche.