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Comment
. 2017 Feb 16;18(1):31.
doi: 10.1186/s13059-017-1170-x.

Mouse genomic screen reveals novel host regulator of metastasis

Toni Celià-Terrassa  1 , Yibin Kang  2
Affiliations
Comment

Mouse genomic screen reveals novel host regulator of metastasis

Toni Celià-Terrassa et al. Genome Biol. .

Abstract

Tumor cells have to overcome challenges in the host tissue microenvironment to metastasize successfully to distant organs. In a recent Nature study, a genome-wide functional screen demonstrated that deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased immune-mediated cell killing by T cells and natural killer (NK) cells, thereby suppressing metastatic colonization.

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Figures

Fig. 1
Fig. 1
Endothelial SPNS2 regulates lymphocyte trafficking to influence metastatic colonization. After extravasation into the lung parenchyma following dissemination through vascular or lymphatic systems, cancer cells normally encounter a hostile environment dominated by immune defenses. In wild-type mice (left panel), the S1P transporter SPNS2 regulates the circulation levels of S1P and maintains lymphocyte trafficking homeostasis as well as organ regulatory T (T reg) cells. In this scenario, the Treg cells are abundant in the lung tissue, which facilitates the colonization of highly metastatic tumor cells. However, in the Spns2-deficient mice (Spns2 tm1a/tm1a; right panel), S1P levels are decreased in circulation but are higher in the lungs, disrupting lymphocyte trafficking. This results in an increased ratio of cytotoxic CD8+ T cells and natural killer (NK) cells in the lungs, which prevents metastatic colonization of arriving cancer cells
See this image and copyright information in PMC

Comment on

  • Genome-wide in vivo screen identifies novel host regulators of metastatic colonization.
    van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H, Griggs N, Velasco-Herrera MD, Tüting T, Sansom OJ, Karp NA, Clare S, Gleeson D, Ryder E, Galli A, Tuck E, Cambridge EL, Voet T, Macaulay IC, Wong K; Sanger Mouse Genetics Project; Spiegel S, Speak AO, Adams DJ. van der Weyden L, et al. Nature. 2017 Jan 12;541(7636):233-236. doi: 10.1038/nature20792. Epub 2017 Jan 4. Nature. 2017. PMID: 28052056 Free PMC article.

References

    1. Celia-Terrassa T, Kang Y. Distinctive properties of metastasis-initiating cells. Genes Dev. 2016;30:892–908. doi: 10.1101/gad.277681.116. - DOI - PMC - PubMed
    1. Lifsted T, Le Voyer T, Williams M, Muller W, Klein-Szanto A, Buetow KH, et al. Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int J Cancer. 1998;77:640–4. doi: 10.1002/(SICI)1097-0215(19980812)77:4<640::AID-IJC26>3.0.CO;2-8. - DOI - PubMed
    1. van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H, Griggs N, et al. Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. Nature. 2017;541:233–6. doi: 10.1038/nature20792. - DOI - PMC - PubMed
    1. Clever D, Roychoudhuri R, Constantinides MG, Askenase MH, Sukumar M, Klebanoff CA, et al. Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche. Cell. 2016;166:1117–31. doi: 10.1016/j.cell.2016.07.032. - DOI - PMC - PubMed
    1. Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, et al. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014;507:508–12. doi: 10.1038/nature12998. - DOI - PMC - PubMed

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