Skip to main content

Vascular co-option in brain metastasis

Abstract

Vascular co-option by brain metastasis-initiating cells has been demonstrated as a critical step in organ colonization. The physical interaction between the cancer cell and the endothelial cell is mediated by integrins and L1CAM and could be involved in aggressive growth but also latency and immune evasion. The key involvement of vascular co-option in brain metastasis has created an emerging field that aims to identify critical targets as well as effective inhibitors with the goal of preventing brain metastases.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D et al (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284(5422):1994–1998

    CAS  Article  Google Scholar 

  2. Kienast Y, Von Baumgarten L, Fuhrmann M, Klinkert WEF, Goldbrunner R, Herms J et al (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16(1):116

    CAS  Article  Google Scholar 

  3. Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH-F, Lee DJ et al (2014) Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156(5):1002–1016

    CAS  Article  Google Scholar 

  4. Er EE, Valiente M, Ganesh K, Zou Y, Agrawal S, Hu J et al (2018) Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat Cell Biol 20:966

    CAS  Article  Google Scholar 

  5. Lorger M, Felding-Habermann B (2010) Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol 176(6):2958–2971

    Article  Google Scholar 

  6. Bentolila LA, Prakash R, Mihic-Probst D, Wadehra M, Kleinman HK, Carmichael TS et al (2016) Imaging of angiotropism/vascular co-option in a murine model of brain melanoma: implications for melanoma progression along extravascular pathways. Sci Rep 6:23834

    CAS  Article  Google Scholar 

  7. Nguyen DX, Chiang AC, Zhang XH-F, Kim JY, Kris MG, Ladanyi M et al (2009) WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell 138(1):51–62

    CAS  Article  Google Scholar 

  8. Ilhan-Mutlu A, Osswald M, Liao Y, Gömmel M, Reck M, Miles D et al (2016) Bevacizumab prevents brain metastases formation in lung adenocarcinoma. Mol Cancer Ther 15:702–710

    CAS  Article  Google Scholar 

  9. Ilhan-Mutlu A, Siehs C, Berghoff AS, Ricken G, Widhalm G, Wagner L et al (2016) Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma. Tumor Biol 37(1):1173–1182

    CAS  Article  Google Scholar 

  10. Frentzas S, Simoneau E, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E et al (2016) Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med 22:1294. https://doi.org/10.1038/nm.4197

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Reynolds AR, Bar-Zion A, Lee CR, Kuczynski EA, Foster FS, Daley F et al (2016) Co-option of Liver vessels and not sprouting angiogenesis drives acquired Sorafenib resistance in hepatocellular carcinoma. JNCI J Natl Cancer Inst. https://doi.org/10.1093/jnci/djw030

    Article  PubMed  Google Scholar 

  12. Bridgeman VL, Vermeulen PB, Foo S, Bilecz A, Daley F, Kostaras E et al (2017) Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models. J Pathol 241(3):362–374. https://doi.org/10.1002/path.4845

    CAS  Article  PubMed  Google Scholar 

  13. Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, Ellis LM et al (2000) Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res 60(17):4959–4967

    CAS  PubMed  Google Scholar 

  14. Jubb AM, Cesario A, Ferguson M, Congedo MT, Gatter KC, Lococo F et al (2011) Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases. Br J Cancer 104:1877. https://doi.org/10.1038/bjc.2011.147

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Carbonell WS, Ansorge O, Sibson N, Muschel R (2009) The vascular basement membrane as “soil” in brain metastasis. PLoS ONE 4(6):e5857

    Article  Google Scholar 

  16. Lorenz L, Axnick J, Buschmann T, Henning C, Urner S, Fang S et al (2018) Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival. Nature 562(7725):128–132. https://doi.org/10.1038/s41586-018-0522-3

    CAS  Article  PubMed  Google Scholar 

  17. Rafii S, Butler JM, Ding B-S (2016) Angiocrine functions of organ-specific endothelial cells. Nature 529:316. https://doi.org/10.1038/nature17040

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Lu J, Ye X, Fan F, Xia L, Bhattacharya R, Bellister S et al (2013) Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of jagged-1. Cancer Cell 23(2):171–185

    CAS  Article  Google Scholar 

  19. Wieland E, Rodriguez-Vita J, Liebler SS, Mogler C, Moll I, Herberich SE et al (2017) Endothelial Notch1 activity facilitates metastasis. Cancer Cell 31(3):355–367

    CAS  Article  Google Scholar 

  20. Beck B, Driessens G, Goossens S, Youssef KK, Kuchnio A, Caauwe A et al (2011) A vascular niche and a VEGF–Nrp1 loop regulate the initiation and stemness of skin tumours. Nature 478(7369):399

    CAS  Article  Google Scholar 

  21. Cao Z, Ding B-S, Guo P, Lee SB, Butler JM, Casey SC et al (2014) Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell 25(3):350–365

    CAS  Article  Google Scholar 

  22. Fan J, Cai B, Zeng M, Hao Y, Giancotti FG, Fu BM (2011) Integrin β4 signaling promotes mammary tumor cell adhesion to brain microvascular endothelium by inducing ErbB2-mediated secretion of VEGF. Ann Biomed Eng 39(8):2223–2241

    Article  Google Scholar 

  23. Yao H, Price TT, Cantelli G, Ngo B, Warner MJ, Olivere L et al (2018) Leukaemia hijacks a neural mechanism to invade the central nervous system. Nature 560(7716):55–60. https://doi.org/10.1038/s41586-018-0342-5

    CAS  Article  PubMed  Google Scholar 

  24. Wiencken-Barger AE, Mavity-Hudson J, Bartsch U, Schachner M, Casagrande VA (2004) The role of L1 in axon pathfinding and fasciculation. Cereb Cortex 14(2):121–131

    CAS  Article  Google Scholar 

  25. Felding-Habermann B, Silletti S, Mei F, Siu C-H, Yip PM, Brooks PC et al (1997) A single immunoglobulin-like domain of the human neural cell adhesion molecule L1 supports adhesion by multiple vascular and platelet integrins. J Cell Biol 139(6):1567–1581

    CAS  Article  Google Scholar 

  26. Donier E, Gomez-Sanchez JA, Grijota-Martinez C, Lakomá J, Baars S, Garcia-Alonso L et al (2012) L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling. PLoS ONE 7(7):e40674

    CAS  Article  Google Scholar 

  27. Kulahin N, Li S, Hinsby A, Kiselyov V, Berezin V, Bock E (2008) Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor. Mol Cell Neurosci 37(3):528–536

    CAS  Article  Google Scholar 

  28. Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H et al (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15(7):807

    CAS  Article  Google Scholar 

  29. Malladi S, Macalinao DG, Jin X, He L, Basnet H, Zou Y et al (2016) Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165(1):45–60

    CAS  Article  Google Scholar 

  30. Gao H, Chakraborty G, Zhang Z, Akalay I, Gadiya M, Gao Y et al (2016) Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling. Cell 166(1):47–62

    CAS  Article  Google Scholar 

  31. Berghoff AS, Rajky O, Winkler F, Bartsch R, Furtner J, Hainfellner JA et al (2013) Invasion patterns in brain metastases of solid cancers. Neuro Oncol 15(12):1664–1672

    Article  Google Scholar 

  32. Soria J-C, Mauguen A, Reck M, Sandler AB, Saijo N, Johnson DH et al (2012) Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 24(1):20–30

    Article  Google Scholar 

  33. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V et al (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non–small-cell lung cancer: AVAiL. J Clin Oncol 27(8):1227–1234

    CAS  Article  Google Scholar 

  34. Jain RK (2014) Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell 26(5):605–622

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Research in the Brain Metastasis Group is supported by MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb-Melanoma Research Alliance Young Investigator Award (498103) (M.V.), Beug Foundation’s Prize for Metastasis Research (M.V.), Fundación Ramón Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), CLIP Award Cancer Research Institute (54545) (M.V.), and AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.). P.G-G. is the recipient of La Caixa Foundation (ID100010434) and European Union´s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement (No. 713673) PhD Program Fellowship (LCF/BQ/IN17/11620028). M.V. is a Ramón y Cajal Investigator (RYC-2013-13365) and EMBO YIP (4053).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manuel Valiente.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

García-Gómez, P., Valiente, M. Vascular co-option in brain metastasis. Angiogenesis 23, 3–8 (2020). https://doi.org/10.1007/s10456-019-09693-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10456-019-09693-x

Keywords

  • Brain metastasis
  • Capillaries
  • Breast cancer
  • Lung cancer
  • Melanoma
  • Vascular co-option