Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, 20007, USA.
Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Sci Rep. 2017 Sep 12;7(1):11410. doi: 10.1038/s41598-017-11764-2.
Adenoid cystic carcinomas (ACC) are rare salivary gland cancers with a high incidence of metastases. In order to study this tumor type, a reliable model system exhibiting the molecular features of this tumor is critical, but none exists, thereby inhibiting in-vitro studies and the analysis of metastatic behavior. To address this deficiency, we have coupled an efficient method to establish tumor cell cultures, conditional reprogramming (CR), with a rapid, reproducible and robust in-vivo zebrafish model. We have established cell cultures from two individual ACC PDX tumors that maintain the characteristic MYB translocation. Additional mutations found in one ACC culture also seen in the PDX tumor. Finally, the CR/zebrafish model mirrors the PDX mouse model and identifies regorafenib as a potential therapeutic drug to treat this cancer type that mimic the drug sensitivity profile in PDX model, further confirming the unique advantages of multiplex system.
腺样囊性癌 (ACC) 是一种罕见的唾液腺癌，具有较高的转移发生率。为了研究这种肿瘤类型，需要一个具有该肿瘤分子特征的可靠模型系统，但目前尚不存在，从而抑制了体外研究和转移行为的分析。为了解决这一不足，我们将一种有效的肿瘤细胞培养方法——条件重编程 (CR) 与快速、可重复和稳健的活体斑马鱼模型相结合。我们已经从两个具有特征性 MYB 易位的个体 ACC PDX 肿瘤中建立了细胞培养物。在一个 ACC 培养物中发现的其他突变也在 PDX 肿瘤中观察到。最后，CR/斑马鱼模型反映了 PDX 小鼠模型，并确定regorafenib 是一种潜在的治疗这种癌症类型的药物，其对该药物的敏感性与 PDX 模型相似，进一步证实了该多重组系统的独特优势。
