Metastatic Colonization by Circulating Tumour Cells

Overview

Journal Nature

Specialty Science

Date 2016 Jan 22

PMID 26791720

Citations 940

Authors

Joan Massague

Anna C Obenauf

Affiliations

Soon will be listed here.

Abstract

Metastasis is the main cause of death in people with cancer. To colonize distant organs, circulating tumour cells must overcome many obstacles through mechanisms that we are only now starting to understand. These include infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds and eventually breaking out to replace the host tissue. They make metastasis a highly inefficient process. However, once metastases have been established, current treatments frequently fail to provide durable responses. An improved understanding of the mechanistic determinants of such colonization is needed to better prevent and treat metastatic cancer.

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References

Minn A, Gupta G, Siegel P, Bos P, Shu W, Giri D . Genes that mediate breast cancer metastasis to lung. Nature. 2005; 436(7050):518-24. PMC: 1283098. DOI: 10.1038/nature03799. View

Urosevic J, Garcia-Albeniz X, Planet E, Real S, Cespedes M, Guiu M . Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH. Nat Cell Biol. 2014; 16(7):685-94. DOI: 10.1038/ncb2977. View

Cao Z, Ding B, Guo P, Lee S, Butler J, Casey S . Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell. 2014; 25(3):350-65. PMC: 4017921. DOI: 10.1016/j.ccr.2014.02.005. View

Campbell P, Yachida S, Mudie L, Stephens P, Pleasance E, Stebbings L . The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010; 467(7319):1109-13. PMC: 3137369. DOI: 10.1038/nature09460. View

Robinson D, Van Allen E, Wu Y, Schultz N, Lonigro R, Mosquera J . Integrative clinical genomics of advanced prostate cancer. Cell. 2015; 161(5):1215-1228. PMC: 4484602. DOI: 10.1016/j.cell.2015.05.001. View

Ma L, Teruya-Feldstein J, Weinberg R . Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007; 449(7163):682-8. DOI: 10.1038/nature06174. View

Magnon C, Hall S, Lin J, Xue X, Gerber L, Freedland S . Autonomic nerve development contributes to prostate cancer progression. Science. 2013; 341(6142):1236361. DOI: 10.1126/science.1236361. View

Weis S, Cui J, Barnes L, Cheresh D . Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol. 2004; 167(2):223-9. PMC: 2172541. DOI: 10.1083/jcb.200408130. View

Milsom C, Lee C, Hackl C, Man S, Kerbel R . Differential post-surgical metastasis and survival in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null) mice with parental and subline variants of human breast cancer: implications for host defense mechanisms regulating metastasis. PLoS One. 2013; 8(8):e71270. PMC: 3743873. DOI: 10.1371/journal.pone.0071270. View

10.

Aceto N, Bardia A, Miyamoto D, Donaldson M, Wittner B, Spencer J . Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014; 158(5):1110-1122. PMC: 4149753. DOI: 10.1016/j.cell.2014.07.013. View

11.

Korpal M, Ell B, Buffa F, Ibrahim T, Blanco M, Celia-Terrassa T . Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011; 17(9):1101-8. PMC: 3169707. DOI: 10.1038/nm.2401. View

12.

Gao H, Chakraborty G, Lee-Lim A, Mo Q, Decker M, Vonica A . The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell. 2012; 150(4):764-79. PMC: 3711709. DOI: 10.1016/j.cell.2012.06.035. View

13.

Kobayashi A, Okuda H, Xing F, Pandey P, Watabe M, Hirota S . Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med. 2011; 208(13):2641-55. PMC: 3244043. DOI: 10.1084/jem.20110840. View

14.

Chen J, Li Y, Yu T, McKay R, Burns D, Kernie S . A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012; 488(7412):522-6. PMC: 3427400. DOI: 10.1038/nature11287. View

15.

Huang Q, Li F, Liu X, Li W, Shi W, Liu F . Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med. 2011; 17(7):860-6. PMC: 3132290. DOI: 10.1038/nm.2385. View

16.

Gilbert L, Hemann M . DNA damage-mediated induction of a chemoresistant niche. Cell. 2010; 143(3):355-66. PMC: 2972353. DOI: 10.1016/j.cell.2010.09.043. View

17.

Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert W, Goldbrunner R, Herms J . Real-time imaging reveals the single steps of brain metastasis formation. Nat Med. 2009; 16(1):116-22. DOI: 10.1038/nm.2072. View

18.

Oskarsson T, Batlle E, Massague J . Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell. 2014; 14(3):306-21. PMC: 3998185. DOI: 10.1016/j.stem.2014.02.002. View

19.

Obenauf A, Massague J . Surviving at a Distance: Organ-Specific Metastasis. Trends Cancer. 2017; 1(1):76-91. PMC: 4673677. DOI: 10.1016/j.trecan.2015.07.009. View

20.

Smyth M, Thia K, Cretney E, Kelly J, Snook M, Forbes C . Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol. 1999; 162(11):6658-62. View