麻省理工学院Matthew G. Vander Heiden小组取得一项新突破。他们开发出乳腺癌器官特异性转移的营养需求。相关论文于2026年1月7日发表在《自然》杂志上。

在这里，该研究组量化了小鼠多个组织中124种代谢物的绝对水平，并研究了这与乳腺癌细胞在不同器官中生长的能力之间的关系。课题组设计了具有广泛转移潜力的乳腺癌细胞，使其对特定营养物质具有营养缺陷，并评估了它们在不同组织部位定植的能力。然后该研究组询问肿瘤在不同组织中的生长与营养可利用性和肿瘤的生物合成活性之间的关系。研究组发现单一的营养物质本身并不能确定乳腺癌细胞可以转移生长的部位。

此外，小组确定嘌呤合成是肿瘤在许多组织中生长和转移的必要条件，并发现这种表型与组织核苷酸可用性或肿瘤从头合成核苷酸活性无关。这些数据表明，微环境中多种营养物质之间的复杂相互作用决定了转移性癌症生长的潜在位点，并强调了外在环境因素与内在细胞特性之间的相互依存关系，这些因素影响着乳腺癌细胞的转移生长。

研究人员表示，癌症转移是导致患者发病率和死亡率的主要因素，然而，决定癌症可以转移到哪些器官的因素尚不完全清楚。

附：英文原文

Title: Nutrient requirements of organ-specific metastasis in breast cancer

Author: Abbott, Keene L., Subudhi, Sonu, Ferreira, Raphael, Gltekin, Yeti, Steinbuch, Sophie C., Munim, Muhammad Bin, Ramesh, Diya L., Honeder, Sophie E., Kumar, Ashwin S., Wu, Michelle, Hansen, Jacob A., Shevzov-Zebrun, Anna, Rashan, Edrees H., Eghbalian, Kian M., Sivanand, Sharanya, Barbeau, Anna M., Riedmayr, Lisa M., Duquette, Mark, Ali, Ahmed, Henning, Nicole, Trojan, Sonia E., Waite, Millenia, Kunchok, Tenzin, Nakano, Mayu A., Gourgue, Florian, Ferraro, Gino B., Do, Brian T., Spanoudaki, Virginia, Snchez-Rivera, Francisco J., Jin, Xin, Church, George M., Jain, Rakesh K., Vander Heiden, Matthew G.

Issue&Volume: 2026-01-07

Abstract: Cancer metastasis is a major contributor to patient morbidity and mortality1, yet the factors that determine the organs where cancers can metastasize are incompletely understood. Here we quantify the absolute levels of 124 metabolites in multiple tissues in mice and investigate how this relates to the ability of breast cancer cells to grow in different organs. We engineered breast cancer cells with broad metastatic potential to be auxotrophic for specific nutrients and assessed their ability to colonize different tissue sites. We then asked how tumour growth in different tissues relates to nutrient availability and tumour biosynthetic activity. We find that single nutrients alone do not define the sites where breast cancer cells can grow as metastases. In addition, we identify purine synthesis as a requirement for tumour growth and metastasis across many tissues and find that this phenotype is independent of tissue nucleotide availability or tumour de novo nucleotide synthesis activity. These data suggest that a complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth, and highlights the interdependence between extrinsic environmental factors and intrinsic cellular properties in influencing where breast cancer cells can grow as metastases.

DOI: 10.1038/s41586-025-09898-9

Source: https://www.nature.com/articles/s41586-025-09898-9