Wagner Benedikt J, Ettner-Sitter Andreas, Ihlo Nicolas A, Behr Merle, Koelbl Sebastian, Brunner Stefan M, Weber Florian, Rau Bettina M, Schlitt Hans J, Brochhausen Christoph, Schoenmehl Rebecca, Artinger Annalena, Schott Dorothea, Pizon Monika, Pachmann Katharina, Aung Thiha, Haerteis Silke, Hackl Christina
Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Bavarian Cancer Research Center (BZKF), University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Sci Rep. 2025 Jan 23;15(1):2896. doi: 10.1038/s41598-025-87054-z.
Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation-circulating cancer stem cells (cCSCs) - is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study. The number of tumorspheres and CETCs/CTCs was analyzed perioperatively in 25 pancreatic cancer patients. Additionally, an individual in vivo chorioallantoic membrane (CAM) culture system was used to generate PDXs from these tumorspheres. While overall correlations of CETCs/CTCs with clinicopathological parameters did not reach statistical significance, a significant difference in the number of tumorspheres was observed between patient subgroups with lower and higher UICC stages. This finding underscores their potential as biomarkers, providing valuable insights into clinical decision-making and tumor progression. The application of tumorspheres on the CAM successfully established PDXs within 7 days. These xenografts closely resembled the histological features of the primary tumor. Hence, this model represents a novel and fast option for individualized testing of new therapies for PDAC.
患者来源的异种移植瘤（PDXs）为胰腺癌精准医学治疗策略的开发提供了生物学相关模型和潜在平台。此外，循环上皮肿瘤细胞（CETCs/CTCs）由实体瘤释放到血液中，一种罕见的亚群——循环癌干细胞（cCSCs）——被认为是复发的原因，并且在转移中起关键作用。为了鉴定cCSCs，本研究建立了一种创新的体外肿瘤球生成检测方法。对25例胰腺癌患者围手术期的肿瘤球数量和CETCs/CTCs进行了分析。此外，使用个体体内鸡胚绒毛尿囊膜（CAM）培养系统从这些肿瘤球中生成PDXs。虽然CETCs/CTCs与临床病理参数的总体相关性未达到统计学意义，但在UICC分期较低和较高的患者亚组之间观察到肿瘤球数量存在显著差异。这一发现强调了它们作为生物标志物的潜力，为临床决策和肿瘤进展提供了有价值的见解。肿瘤球在CAM上的应用在7天内成功建立了PDXs。这些异种移植瘤与原发肿瘤的组织学特征非常相似。因此，该模型代表了一种用于胰腺癌新疗法个体化测试的新颖且快速的选择。
