Increased exposure of anionic phospholipids on the surface of tumor blood vessels

Sophia Ran, Amber Downes, Philip E. Thorpe

Research output: Contribution to journalArticle

340 Citations (Scopus)

Abstract

Anionic phospholipids are largely absent from the external leaflet of the plasma membrane of mammalian cells under normal conditions. Exposure of phosphatidylserine on the cell surface occurs during apoptosis, necrosis, cell injury, cell activation, and malignant transformation. In the present study, we determined whether anionic phospholipids become exposed on tumor vasculature. A monoclonal antibody, 9D2, which specifically recognizes anionic phospholipids, was injected into mice bearing a variety of orthotopic or ectopic tumors. Other mice received annexin V, a natural ligand that binds to anionic phospholipids. Both 9D2 and annexin V specifically localized to vascular endothelium in all of the tumors, and also to tumor cells in and around regions of necrosis. Between 15 and 40% of endothelial cells in tumor vessels were stained. No localization was detected on normal endothelium. Various factors and tumor-associated conditions known to be present in the tumor microenvironment were examined for their ability to cause exposure of anionic phospholipids in cultured endothelial cells, as judged by 9D2 and annexin V binding. Hypoxia/reoxygenation, acidity, thrombin, and inflammatory cytokines all induced exposure of anionic phospholipids. Hydrogen peroxide was also a strong inducer. Combined treatment with inflammatory cytokines and hypoxia/reoxygenation had greater than additive effects. Possibly, injury and activation of tumor endothelium by cytokines and reactive oxygen species induce exposure of anionic phospholipids, most likely phosphatidylserine. Anionic phospholipids on tumor vessels could potentially provide markers for tumor vessel targeting and imaging.

Original languageEnglish (US)
Pages (from-to)6132-6140
Number of pages9
JournalCancer Research
Volume62
Issue number21
StatePublished - Nov 1 2002

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Vascular Tissue Neoplasms
Phospholipids
Annexin A5
Neoplasms
Phosphatidylserines
Cytokines
Endothelium
Necrosis
Endothelial Cells
Tumor Microenvironment
Vascular Endothelium
Wounds and Injuries
Tumor Biomarkers
Thrombin
Hydrogen Peroxide
Cultured Cells
Reactive Oxygen Species
Monoclonal Antibodies
Cell Membrane
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ran, S., Downes, A., & Thorpe, P. E. (2002). Increased exposure of anionic phospholipids on the surface of tumor blood vessels. Cancer Research, 62(21), 6132-6140.

Increased exposure of anionic phospholipids on the surface of tumor blood vessels. / Ran, Sophia; Downes, Amber; Thorpe, Philip E.

In: Cancer Research, Vol. 62, No. 21, 01.11.2002, p. 6132-6140.

Research output: Contribution to journalArticle

Ran, S, Downes, A & Thorpe, PE 2002, 'Increased exposure of anionic phospholipids on the surface of tumor blood vessels', Cancer Research, vol. 62, no. 21, pp. 6132-6140.
Ran, Sophia ; Downes, Amber ; Thorpe, Philip E. / Increased exposure of anionic phospholipids on the surface of tumor blood vessels. In: Cancer Research. 2002 ; Vol. 62, No. 21. pp. 6132-6140.
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