Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Metab. 2024 Sep;6(9):1668-1681. doi: 10.1038/s42255-024-01105-9. Epub 2024 Aug 19.
Metastases arise from subsets of cancer cells that disseminate from the primary tumour. The ability of cancer cells to thrive in a new tissue site is influenced by genetic and epigenetic changes that are important for disease initiation and progression, but these factors alone do not predict if and where cancers metastasize. Specific cancer types metastasize to consistent subsets of tissues, suggesting that primary tumour-associated factors influence where cancers can grow. We find primary and metastatic pancreatic tumours have metabolic similarities and that the tumour-initiating capacity and proliferation of both primary-derived and metastasis-derived cells is favoured in the primary site relative to the metastatic site. Moreover, propagating cells as tumours in the lung or the liver does not enhance their relative ability to form large tumours in those sites, change their preference to grow in the primary site, nor stably alter aspects of their metabolism relative to primary tumours. Primary liver and lung cancer cells also exhibit a preference to grow in their primary site relative to metastatic sites. These data suggest cancer tissue of origin influences both primary and metastatic tumour metabolism and may impact where cancer cells can metastasize.
转移瘤来源于从原发性肿瘤中扩散出来的癌细胞亚群。癌细胞在新的组织部位生长的能力受到遗传和表观遗传变化的影响，这些变化对疾病的发生和发展很重要，但这些因素本身并不能预测癌症是否以及在何处转移。特定类型的癌症转移到一致的组织亚群，这表明原发性肿瘤相关因素影响着癌症的生长部位。我们发现原发和转移性胰腺肿瘤具有代谢相似性，并且原发衍生和转移衍生细胞的肿瘤起始能力和增殖在原发性肿瘤部位相对于转移性肿瘤部位更有利。此外，在肺部或肝脏中作为肿瘤繁殖的细胞不会增强它们在这些部位形成大肿瘤的相对能力，改变它们在原发性肿瘤部位生长的偏好，也不会稳定地改变它们相对于原发性肿瘤的代谢方面。原发性肝癌和肺癌细胞也表现出相对于转移性肿瘤部位，在原发性肿瘤部位生长的偏好。这些数据表明，癌症的组织来源既影响原发性肿瘤，也影响转移性肿瘤的代谢，并可能影响癌细胞的转移部位。
