Abstract P3-08-11: Establishing Breast Cancer Patient-derived Xenografts from circulating cancer stem cells in the chorioallantoic membrane (CAM) Model

Abstract

Abstract Background: Circulating cancer stem cells (cCSCs) are a small aggressive subset of circulating tumor cells with cancer stem cells features: resistance to diverse cancer treatments and the capacity for generating new metastases. Patient-derived xenografts (PDX) are an increasingly accepted tool in oncology, providing biologically meaningful models of many cancer types, and potential platforms for the development of precision oncology approaches. Commonly, mouse models are used for the xenotransplant assessment of potential new therapeutic targets in cancers. However, animal models do not necessarily represent the real world scenario and are costly and time consuming. An attractive alternative to such animal experiments is the chicken chorioallantoic membrane (CAM) assay. CAM assay is increasingly used as a rapid cost-effective in vivo drug-testing platform that recapitulates many aspects of human cancers. Methods: In this study, primary cultures from circulating cancer stem cells were established using sphere-forming assays. Subsequently, tumorspheres were transplanted onto the CAM membrane of fertilized chicken eggs to form secondary microtumors. Histopathological analyses were performed to confirm that the CAM tumor had the original morphological profile of the patient tumor. Results: We have developed an innovative reliable in vitro platform for cultivation of CSCs from peripheral blood of breast cancer patients. The number of tumorspheres increased significantly with tumor progression. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p< 0.05). Patients with multiple metastases had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p< 0.05). The number of tumorspheres was positively correlated with Ki-67, Her2 status and grade score in primary breast tumors. Tumorspheres showed self-renewal, growth potential, invasion and differentiation in vivo. Tumorspheres could be successfully grafted onto the CAM and grafting positively correlated with aggressiveness and proliferation capacity of the primary tumor. These tumors growing on the CAM pathologically closely resembled the primary tumor. Conclusion: The number of tumorspheres cultured from peripheral blood of cancer patients and the success rate of establishing PDX directly reflect the aggressiveness and proliferation capacity of the primary tumor. Our results support the CAM model using cCSC as a valuable alternative for xenotransplant models. It allows the establishment of new PDXs and provides a fast, cost-effective, and easy to use preclinical platform for cancer biology research, new drug development, treatment individualization, and biomarker discovery. Citation Format: Monika PIZON, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. Establishing Breast Cancer Patient-derived Xenografts from circulating cancer stem cells in the chorioallantoic membrane (CAM) Model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-08-11.