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Collective metastasis: coordinating the multicellular voyage

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Abstract

The metastatic process is arduous. Cancer cells must escape the confines of the primary tumor, make their way into and travel through the circulation, then survive and proliferate in unfavorable microenvironments. A key question is how cancer cells overcome these multiple barriers to orchestrate distant organ colonization. Accumulating evidence in human patients and animal models supports the hypothesis that clusters of tumor cells can complete the entire metastatic journey in a process referred to as collective metastasis. Here we highlight recent studies unraveling how multicellular coordination, via both physical and biochemical coupling of cells, induces cooperative properties advantageous for the completion of metastasis. We discuss conceptual challenges and unique mechanisms arising from collective dissemination that are distinct from single cell-based metastasis. Finally, we consider how the dissection of molecular transitions regulating collective metastasis could offer potential insight into cancer therapy.

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Funding

The Department of Defense Breast Cancer Research Program (BCRP; W81XWH-18–1–0098), the NIH/NCI (R37CA234488), Susan G. Komen Foundation (Career Catalyst Research Grant), and the Burroughs Wellcome Fund Career Award for Medical Scientists.

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  1. Translational Research Program, Public Health Sciences and Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Emma Wrenn, Yin Huang & Kevin Cheung

  2. Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, 98195, USA

    Emma Wrenn

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  1. Emma Wrenn
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Correspondence to Kevin Cheung.

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EDW and KJC are inventors on a pending patent application related to collective metastasis by tumor cell clusters.

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Wrenn, E., Huang, Y. & Cheung, K. Collective metastasis: coordinating the multicellular voyage. Clin Exp Metastasis 38, 373–399 (2021). https://doi.org/10.1007/s10585-021-10111-0

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