Crossing the Endothelial Barrier During Metastasis

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2013 Nov 23

PMID 24263189

Citations 438

Authors

Nicolas Reymond

Barbara Borda DAgua

Anne J Ridley

Affiliations

Soon will be listed here.

Abstract

During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.

Citing Articles

KRT7 promotes pancreatic cancer metastasis by remodeling the extracellular matrix niche through FGF2-fibroblast crosstalk.

Jiang Y, Liao C, Lai J, Peng Y, Chen Q, Zheng X Sci Rep. 2025; 15(1):6951.

PMID: 40011455 PMC: 11865440. DOI: 10.1038/s41598-024-84129-1.

CircAKT3 promotes prostate cancer proliferation and metastasis by enhancing the binding of RPS27A and RPL11.

Song X, Wei Z, Zhang C, Han D, Liu J, Song Y Mol Cancer. 2025; 24(1):53.

PMID: 39994725 PMC: 11852832. DOI: 10.1186/s12943-025-02261-6.

Tumor microbiome: roles in tumor initiation, progression, and therapy.

Zhang S, Huang J, Jiang Z, Tong H, Ma X, Liu Y Mol Biomed. 2025; 6(1):9.

PMID: 39921821 PMC: 11807048. DOI: 10.1186/s43556-025-00248-9.

N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex.

Moazzeni S, Kyker-Snowman K, Cohen R, Wang H, Li R, Shreiber D Sci Rep. 2025; 15(1):4296.

PMID: 39905109 PMC: 11794589. DOI: 10.1038/s41598-025-88537-9.

Navigating PROTACs in Cancer Therapy: Advancements, Challenges, and Future Horizons.

Ibrahim S, Khan M, Khurram I, Rehman R, Rauf A, Ahmad Z Food Sci Nutr. 2025; 13(2):e70011.

PMID: 39898116 PMC: 11786021. DOI: 10.1002/fsn3.70011.

References

Karpatkin S, Pearlstein E, Ambrogio C, Coller B . Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest. 1988; 81(4):1012-9. PMC: 329625. DOI: 10.1172/JCI113411. View

Schumacher D, Strilic B, Sivaraj K, Wettschureck N, Offermanns S . Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell. 2013; 24(1):130-7. DOI: 10.1016/j.ccr.2013.05.008. View

Anderberg C, Cunha S, Zhai Z, Cortez E, Pardali E, Johnson J . Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination. J Exp Med. 2013; 210(3):563-79. PMC: 3600899. DOI: 10.1084/jem.20120662. View

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

Chiang A, Massague J . Molecular basis of metastasis. N Engl J Med. 2008; 359(26):2814-23. PMC: 4189180. DOI: 10.1056/NEJMra0805239. View

Dong C, Slattery M, Liang S, Peng H . Melanoma cell extravasation under flow conditions is modulated by leukocytes and endogenously produced interleukin 8. Mol Cell Biomech. 2006; 2(3):145-59. PMC: 2778865. View

Li B, Zhao W, Tan Z, Fang W, Zhu L, Chen Y . Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells. FEBS Lett. 2006; 580(17):4252-60. DOI: 10.1016/j.febslet.2006.06.056. View

Ito S, Nakanishi H, Ikehara Y, Kato T, Kasai Y, Ito K . Real-time observation of micrometastasis formation in the living mouse liver using a green fluorescent protein gene-tagged rat tongue carcinoma cell line. Int J Cancer. 2001; 93(2):212-7. DOI: 10.1002/ijc.1318. View

Kohler S, Ullrich S, Richter U, Schumacher U . E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung. Br J Cancer. 2009; 102(3):602-9. PMC: 2822933. DOI: 10.1038/sj.bjc.6605492. View

10.

Chatterjee M, Sequeira L, Jenkins-Kabaila M, Dubyk C, Pathak S, van Golen K . Individual rac GTPases mediate aspects of prostate cancer cell and bone marrow endothelial cell interactions. J Signal Transduct. 2011; 2011:541851. PMC: 3135208. DOI: 10.1155/2011/541851. View

11.

Drabsch Y, Ten Dijke P . TGF-β signaling in breast cancer cell invasion and bone metastasis. J Mammary Gland Biol Neoplasia. 2011; 16(2):97-108. PMC: 3095797. DOI: 10.1007/s10911-011-9217-1. View

12.

Jeon J, Zervantonakis I, Chung S, Kamm R, Charest J . In vitro model of tumor cell extravasation. PLoS One. 2013; 8(2):e56910. PMC: 3577697. DOI: 10.1371/journal.pone.0056910. View

13.

Yu L, Andrews N, Zhao Q, McKean D, Williams J, Connor L . Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion. J Biol Chem. 2006; 282(1):773-81. DOI: 10.1074/jbc.M606862200. View

14.

Kobayashi H, Boelte K, Lin P . Endothelial cell adhesion molecules and cancer progression. Curr Med Chem. 2007; 14(4):377-86. DOI: 10.2174/092986707779941032. View

15.

Qian B, Pollard J . Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51. PMC: 4994190. DOI: 10.1016/j.cell.2010.03.014. View

16.

Murakami T, Maki W, Cardones A, Fang H, Kyi A, Nestle F . Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Res. 2002; 62(24):7328-34. View

17.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

18.

Wendel C, Hemping-Bovenkerk A, Krasnyanska J, Mees S, Kochetkova M, Stoeppeler S . CXCR4/CXCL12 participate in extravasation of metastasizing breast cancer cells within the liver in a rat model. PLoS One. 2012; 7(1):e30046. PMC: 3258260. DOI: 10.1371/journal.pone.0030046. View

19.

Sampieri K, Fodde R . Cancer stem cells and metastasis. Semin Cancer Biol. 2012; 22(3):187-93. DOI: 10.1016/j.semcancer.2012.03.002. View

20.

Felding-Habermann B, OToole T, Smith J, Fransvea E, Ruggeri Z, Ginsberg M . Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci U S A. 2001; 98(4):1853-8. PMC: 29346. DOI: 10.1073/pnas.98.4.1853. View