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.
癌症转移是导致患者发病和死亡的主要原因之一，但决定癌症转移靶向器官的关键因素仍未完全阐明。本研究通过量化小鼠多组织内124种代谢物的绝对含量，探究其与乳腺癌细胞在不同器官中增殖能力的关联机制。我们构建了具有广谱转移潜能的乳腺癌细胞，使其呈现特定营养缺陷型表型，并评估其在各组织微环境中的定植能力。进一步研究揭示，不同组织部位的肿瘤生长与营养可利用性及肿瘤生物合成活性存在相关性。研究发现单一营养素无法决定乳腺癌细胞的转移性生长位点。此外，我们证实嘌呤合成是肿瘤跨组织生长和转移的必要条件，且该表型与组织核苷酸可利用性及肿瘤核苷酸从头合成活性无关。这些数据表明，微环境中多种营养素的复杂互作决定了转移性癌症的潜在生长位点，同时揭示了外在环境因素与内在细胞特性在调控乳腺癌转移定植中的协同作用。
Nutrient requirements of organ-specific metastasis in breast cancer
肿瘤(癌症)患者之家