Clinical & Experimental Metastasis

, Volume 28, Issue 1, pp 1–12 | Cite as

Platelet adhesion and fusion to endothelial cell facilitate the metastasis of tumor cell in hypoxia-reoxygenation condition

  • Na Zhang
  • Wen-Jian Zhang
  • Han-Qing Cai
  • Hong-Lin Liu
  • Liang Peng
  • Cheng-Hui Li
  • Li-Ya Ye
  • Shi-Qing Xu
  • Zhi-Hua Yang
  • Jin-Ning Lou
Research Paper
First Online:
Received:
Accepted:

Abstract

To investigate the relevant molecular mechanisms of platelet in promoting metastasis of tumor cell. The adhesion of fluorescence dye labeled-platelet to human liver sinusoidal endothelial cell (LSEC) line and tumor cell lines were detected by fluorescence microscope and fluorescence plate reader or laser scanning confocal microscope. The relevant adhesion molecules were analyzed by the antibody blockage experiment. The immune colloidal gold transmission electron microscope (TEM), flow cytometry and dye transfer were used to decipher the adhesion and fusion of platelet and LSEC. The tumor cells adhesion to vessels in ischemia condition was analyzed on mouse mesenteric vessels and the metastasis and neovascularization of metastatic foci in pulmonary tissue were also detected after tumor cells injected into nude mice via tail veil. After hypoxia-reoxygenation, tumor cell or LSEC markedly increased its adhesion with platelet, which could be blocked by different antibodies to platelet adhesion molecules. Platelet increased adhesion of tumor cell to LSEC in dose-dependent manner. The fusion of platelet and LSEC was demonstrated by translocation of fluorescent dye from platelet into the adherent LSEC; gpIIb emerged on the LSEC; and confirmed by TEM. The morphological examination found platelet presented between tumor cell and LSEC. Animal experiment indicated that the tumor adhesion to vessels was seldom in normal condition, but increased in ischemia-reperfusion condition, and further significantly enhanced by platelets. The number of tumor metastatic foci and the density of blood vessels within metastatic foci in lung were markedly increased by tumor cell pre-adhered with platelet. The adhesion or fusion of platelet to endothelial cell mediated by platelet surface adhesion molecules, which could promote the adhesion of tumor cell with endothelial cells and the tumor metastasis.

Keywords

Platelet Liver sinusoidal endothelial cell Tumor cell Metastasis Fusion 

Abbreviations

LSEC

Human liver sinusoidal endothelial cell

TEM

Transmission electron microscope

H–E

Hematoxylin and eosin

ICAM-1

Intercellular adhesion molecule-1

VCAM-1

Vascular cell adhesion molecule-1

ELAM-1

Endothelial leukocyte adhesion molecule-1

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Notes

Acknowledgments

This work was supported by the grants from National Basic Research Program of China to LOU J (2009CB521804) and Beijing Municipal Natural Science Foundation to Cheng-Hui Li (7092093).

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Na Zhang
    • 1
  • Wen-Jian Zhang
    • 2
  • Han-Qing Cai
    • 3
  • Hong-Lin Liu
    • 2
  • Liang Peng
    • 2
  • Cheng-Hui Li
    • 4
  • Li-Ya Ye
    • 2
  • Shi-Qing Xu
    • 2
  • Zhi-Hua Yang
    • 5
  • Jin-Ning Lou
    • 1
    • 2
  1. 1.Graduate School of Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Institute of Clinical Medical SciencesChina-Japan Friendship HospitalBeijingPeople’s Republic of China
  3. 3.Department of EndocrinologyThe Second Hospital of Jilin UniversityChangchunPeople’s Republic of China
  4. 4.Department of AnesthesiologyChina-Japan Friendship HospitalBeijingPeople’s Republic of China
  5. 5.Institute of CancerChinese Academy of Medical SciencesBeijingPeople’s Republic of China

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