科學家繪製出人類腫瘤細胞系的轉移圖譜

科學家繪製出人類腫瘤細胞系的轉移圖譜

作者：

小柯機器人

發布時間：2020/12/12 20:13:51

美國哈佛大學Todd R. Golub、Xin Jin等研究人員合作繪製出人類腫瘤細胞系的轉移圖譜。這一研究成果發表在2020年12月9日出版的國際學術期刊《自然》上。

研究人員報導了一種體內條形碼策略，該策略能夠按比例確定小鼠異種移植物中人類癌細胞系的轉移潛力。研究人員驗證了該方法的穩健性、可擴展性和可重複性，並將其應用於21種實體瘤的500個細胞系。研究人員創建了第一代轉移圖譜（MetMap），揭示了器官特定的轉移模式，使這些模式與臨床和基因組特徵相關聯。

研究人員通過檢測能夠轉移到大腦的乳腺癌分子基礎來證明了MetMap的實用性，這是這類癌症患者的主要死亡原因。能夠轉移到大腦的乳腺癌表現出脂質代謝的改變。這些細胞中脂質代謝的紊亂抑制了腦轉移的進展，提示了一種對抗該疾病的治療策略，並證明了MetMap作為支持轉移研究資源的實用性。

據介紹，大多數癌症死因是通過轉移來導致的，但是由於體內模型的複雜性，大規模的轉移研究一直是不切實際的。

附：英文原文

Title: A metastasis map of human cancer cell lines

Author: Xin Jin, Zelalem Demere, Karthik Nair, Ahmed Ali, Gino B. Ferraro, Ted Natoli, Amy Deik, Lia Petronio, Andrew A. Tang, Cong Zhu, Li Wang, Danny Rosenberg, Vamsi Mangena, Jennifer Roth, Kwanghun Chung, Rakesh K. Jain, Clary B. Clish, Matthew G. Vander Heiden, Todd R. Golub

Issue&Volume: 2020-12-09

Abstract: Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical owing to the complexity of in vivo models. Here we introduce an in vivo barcoding strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale. We validated the robustness, scalability and reproducibility of the method and applied it to 500 cell lines1,2 spanning 21 types of solid tumour. We created a first-generation metastasis map (MetMap) that reveals organ-specific patterns of metastasis, enabling these patterns to be associated with clinical and genomic features. We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain—a principal cause of death in patients with this type of cancer. Breast cancers capable of metastasizing to the brain showed evidence of altered lipid metabolism. Perturbation of lipid metabolism in these cells curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a resource to support metastasis research.

DOI: 10.1038/s41586-020-2969-2

Source: https://www.nature.com/articles/s41586-020-2969-2