Cancer tissue of origin constrains the growth and metabolism of metastases,Nature Metabolism

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Cancer tissue of origin constrains the growth and metabolism of metastases
Nature Metabolism ( IF 18.9 ) Pub Date : 2024-08-19 , DOI: 10.1038/s42255-024-01105-9
Sharanya Sivanand _{1,

2} , Yetis Gultekin _{1,

2} , Peter S Winter _{1,

3,

4,

5} , Sidney Y Vermeulen _{1,

2} , Konstantine M Tchourine ₆ , Keene L Abbott _{1,

2,

4} , Laura V Danai _{1,

2,

7} , Florian Gourgue _{1,

2} , Brian T Do _{1,

5} , Kayla Crowder ₈ , Tenzin Kunchok ₈ , Allison N Lau _{1,

2} , Alicia M Darnell _{1,

2} , Alexandria Jefferson _{1,

2,

8} , Satoru Morita ₉ , Dan G Duda ₉ , Andrew J Aguirre _{3,

4,

10} , Brian M Wolpin ₃ , Nicole Henning _{1,

11} , Virginia Spanoudaki _{1,

11} , Laura Maiorino ₁ , Darrell J Irvine _{1,

12,

13,

14} , Omer H Yilmaz _{1,

2,

4,

15} , Caroline A Lewis _{8,

16} , Dennis Vitkup _{6,

17} , Alex K Shalek _{1,

4,

5,

14,

18} , Matthew G Vander Heiden _{1,

2,

3,

4}

Affiliation

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Systems Biology, Columbia University Medical Center, New York, NY, USA.
Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, MA, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Edwin L Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Preclinical Imaging and Testing Facility, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Ragon Institute of MGH, MITnd Harvard, Cambridge, MA, USA.
Department of Pathology, Massachusetts General Hospital and Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Department of Biomedical Informatics, Columbia University Medical Center, New York, NY, USA.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.

Metastases arise from subsets of cancer cells that disseminate from the primary tumour^1,2. 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^3,4. 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.

中文翻译：

癌组织来源限制了转移灶的生长和代谢

转移源于从原发肿瘤播散的癌细胞亚群^1,2。癌细胞在新组织部位茁壮成长的能力受遗传和表观遗传变化的影响，这些变化对疾病的发生和进展很重要，但仅凭这些因素并不能预测癌症是否转移以及在哪里转移^3,4。特定的癌症类型转移到一致的组织亚群，表明原发性肿瘤相关因素会影响癌症的生长位置。我们发现原发性和转移性胰腺肿瘤具有代谢相似性，并且相对于转移部位，原发性部位和转移性细胞的肿瘤起始能力和增殖在原发部位更有利。此外，在肺或肝脏中将细胞扩增为肿瘤并不会增强它们在这些部位形成大肿瘤的相对能力，不会改变它们在原发部位生长的偏好，也不会稳定地改变它们相对于原发性肿瘤的代谢方面。相对于转移部位，原发性肝癌和肺癌细胞也表现出在其原发部位生长的偏好。这些数据表明，癌组织来源会影响原发性和转移性肿瘤代谢，并可能影响癌细胞的转移位置。

更新日期：2024-08-19

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