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Cancer genomics

Systemic cell–cell communication in cancer

Nature Reviews Genetics volume 26, page 4 (2025)Cite this article

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How does a primary cancer reprogramme secondary organs to orchestrate metastatic dissemination? As a systemic disease, cancer induces functional and compositional changes beyond the tumour, educating the microenvironment within secondary organs to establish pre-metastatic niches — specialized microenvironments that support the seeding and outgrowth of metastatic cancer cells.

In 2005, a fascinating study by Kaplan et al. demonstrated that bone marrow-derived cells (BMDCs) are crucial mediators of pre-metastatic niche formation in future sites of metastasis in several preclinical mouse models of cancer. In response to a growing tumour, BMDCs exit the bone marrow and migrate to the lungs to establish pre-metastatic niches. Only then do cancer cells become detectable in the lungs and metastatic colonization takes place. These observations implicate a communication axis between tumour, bone marrow and secondary organ sites during cancer cell dissemination and survival, which fascinates me as a systems biologist because it suggests an unmet need to investigate cancer at the organism level.

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  • Lummertz da Rocha, E. et al. CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development. Nat. Cell Biol. 24, 579–589 (2022)

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  1. Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis, Brazil

    Edroaldo Lummertz da Rocha

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  1. Edroaldo Lummertz da Rocha
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Correspondence to Edroaldo Lummertz da Rocha.

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Lummertz da Rocha, E. Systemic cell–cell communication in cancer. Nat Rev Genet 26, 4 (2025). https://doi.org/10.1038/s41576-024-00785-z

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