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METASTASIS

Mapping the switch that drives the pre-metastatic niche

Nature Cancer volume 1, pages 577–579 (2020)Cite this article

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The pre-metastatic niche is a complex microenvironment formed by the influence of tumor-derived factors on stromal and immune cells at distant sites of disseminated tumor-cell colonization. Signaling through the kinase p38α and regulation of the type I interferon receptor are now linked to formation of the pre-metastatic niche.

Stromal cells and changes in the matrisome (the extracellular matrix and its components) are paramount to niche formation and contribute to myeloid-cell infiltration. Myeloid-cell recruitment takes place in response to signals from stromal cells that remodel the extracellular matrix and secrete growth factors and cytokines that recruit and instruct immune cells2,3. Myeloid cells are a chief effector of pre-metastatic niche function. Numerous studies have examined myeloid-cell ontogeny and spatiotemporal dynamics in the formation of the pre-metastatic niche4,5,7. The versatile nature of myeloid cells is such that they can induce apoptosis of circulating tumor cells or they can support the colonization, survival and outgrowth of tumor cells by producing leukotrienes, neutrophil extracellular traps or immunosuppressive signals, demonstrative of the broad range of effects that these cells can impart on the regulation of metastatic outgrowth5,7,8. Although much work has focused on the myeloid-cell compartment, stromagenesis that precedes myeloid-cell recruitment in the formation of the pre-metastatic niche has not been as well characterized and may hold important implications for approaches to effectively targeting this niche3.

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Fig. 1: p38a signaling drives pre-metastatic niche formation.

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Authors and Affiliations

  1. Tumor Microenvironment and Metastasis Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Sabina Kaczanowska & Rosandra N. Kaplan

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  1. Sabina Kaczanowska
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  2. Rosandra N. Kaplan
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Correspondence to Rosandra N. Kaplan.

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The authors declare no competing interests.

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Kaczanowska, S., Kaplan, R.N. Mapping the switch that drives the pre-metastatic niche. Nat Cancer 1, 577–579 (2020). https://doi.org/10.1038/s43018-020-0076-9

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