Rousset Xavier, Maillet Denis, Grolleau Emmanuel, Barthelemy David, Calattini Sara, Brevet Marie, Balandier Julie, Raffin Margaux, Geiguer Florence, Garcia Jessica, Decaussin-Petrucci Myriam, Peron Julien, Benzerdjeb Nazim, Couraud Sébastien, Viallet Jean, Payen Léa
INOVOTION, 38700 La Tronche, France.
University Claude Bernard Lyon, 69100 Villeurbanne, France.
Cancers (Basel). 2022 Aug 23;14(17):4085. doi: 10.3390/cancers14174085.
Patient-Derived Xenografts (PDXs) in the Chorioallantoic Membrane (CAM) are a representative model for studying human tumors. Circulating Tumor Cells (CTCs) are involved in cancer dissemination and treatment resistance mechanisms. To facilitate research and deep analysis of these few cells, significant efforts were made to expand them. We evaluated here whether the isolation of fresh CTCs from patients with metastatic cancers could provide a reliable tumor model after a CAM xenograft. We enrolled 35 patients, with breast, prostate, or lung metastatic cancers. We performed microfluidic-based CTC enrichment. After 48-72 h of culture, the CTCs were engrafted onto the CAM of embryonated chicken eggs at day 9 of embryonic development (EDD9). The tumors were resected 9 days after engraftment and histopathological, immunochemical, and genomic analyses were performed. We obtained in ovo tumors for 61% of the patients. Dedifferentiated small tumors with spindle-shaped cells were observed. The epithelial-to-mesenchymal transition of CTCs could explain this phenotype. Beyond the feasibility of NGS in this model, we have highlighted a genomic concordance between the in ovo tumor and the original patient's tumor for constitutional polymorphism and somatic alteration in one patient. Alu DNA sequences were detected in the chicken embryo's distant organs, supporting the idea of dedifferentiated cells with aggressive behavior. To our knowledge, we performed the first chicken CAM CTC-derived xenografts with NGS analysis and evidence of CTC dissemination in the chicken embryo.
绒毛尿囊膜（CAM）中的患者来源异种移植瘤（PDXs）是研究人类肿瘤的代表性模型。循环肿瘤细胞（CTC）参与癌症扩散和治疗抵抗机制。为了便于对这些少量细胞进行研究和深入分析，人们付出了巨大努力来扩增它们。我们在此评估从转移性癌症患者中分离新鲜CTC在CAM异种移植后是否能提供可靠的肿瘤模型。我们招募了35例患有乳腺癌、前列腺癌或肺癌转移的患者。我们进行了基于微流控的CTC富集。培养48 - 72小时后，在胚胎发育第9天（EDD9）将CTC接种到受精鸡蛋的CAM上。移植后9天切除肿瘤，并进行组织病理学、免疫化学和基因组分析。我们为61%的患者获得了卵内肿瘤。观察到具有梭形细胞的去分化小肿瘤。CTC的上皮 - 间质转化可以解释这种表型。除了该模型中NGS的可行性外，我们还强调了在一名患者中卵内肿瘤与原始患者肿瘤在结构多态性和体细胞改变方面的基因组一致性。在鸡胚的远处器官中检测到Alu DNA序列，支持了具有侵袭性的去分化细胞的观点。据我们所知，我们首次进行了带有NGS分析的鸡CAM CTC来源异种移植，并证明了CTC在鸡胚中的扩散。
