Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy

Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8594, USA.
International Journal of Radiation OncologyBiologyPhysics (Impact Factor: 4.18). 01/2003; 54(5):1479-84. DOI: 10.1016/S0360-3016(02)03928-7
Source: PubMed

ABSTRACT (1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment.
Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by 125I-annexin V binding.
Anti-PS antibody bound specifically to vascular endothelium in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelium in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability.
Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might be induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy.

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    • "We reported previously that SapC preferentially interacts with unsaturated, negatively charged phospholipids (such as dioleoylphosphatidylserine, DOPS), at acidic pH [8] [14]. It has been reported that phosphatidylserine (PS) is relatively abundant on the surface of tumor tissues [15] [16]; it could provide a tumor-specific target for SapC. In the design of our new therapeutic agent (SapC-DOPS nanovesicles), we took advantage of two unique properties of tumor cells compared to normal cells. "
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    • "Thus, in addition to imaging apoptotic tumor cells, PS-binding probes also image the exposed PS on the tumor vasculature. We have developed a series of monoclonal antibodies that recognize PS with higher specificity than does annexin V [7] [8] [9] [10]. The antibodies recognize PS complexed with the PS-binding protein, β 2 -glycoprotein 1 (β 2 GP1) [10]. "
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