X-Ray-induced P-selectin Localization to the Lumen of Tumor Blood Vessels

Abstract

P-selectin is a cell adhesion molecule that is sequestered in Weibel-Palade storage reservoirs within the vascular endothelium and α granules in platelets. P-selectin is rapidly translocated to the vascular lumen after tissue injury to initiate the adhesion and activation of platelets and leukocytes. We studied the histological pattern of P-selectin expression in irradiated tumor blood vessels. We observed that P-selectin was localized within the endothelium of tumor vessels prior to treatment. At 1–6 h following irradiation, P-selectin was mobilized to the lumen of blood vessels. To determine whether radiation-induced vascular lumen localization of P-selectin was tumor type specific or species specific, we studied tumors in rats, C3H mice, C57BL6 mice, and nude mice. P-selectin localization to the vascular lumen was present in all tumors and all species studied. Irradiated intracranial gliomas showed P-selectin localization to the vascular lumen within 1 h, whereas blood vessels in normal brain showed no P-selectin staining in the endothelium and no localization to the irradiated vascular lumen. Radiation-induced P-selectin localization to the vascular lumen increased in time-dependent manner, until 24 h after irradiation. P-selectin in platelets may account for the time-dependent increase in staining within the vascular lumen after irradiation. We therefore used immunohistochemistry for platelet antigen GP-IIIa to differentiate between endothelial and platelet localization of P-selectin. We found that GP-IIIa staining was not present at 1 h after irradiation, but it increased at 6 and 24 h. P-selectin localization to the vascular lumen at 6–24 h was, in part, associated with platelet aggregation. These findings indicate that radiation-induced P-selectin staining in the vascular lumen of neoplasms is associated with aggregation of platelets. Radiation-induced localization of P-selectin to the vascular lumen is specific to the microvasculature of malignant gliomas and is not present in the blood vessels of the irradiated normal brain.