X-ray-induced P-selectin localization to the lumen of tumor blood vessels

Cancer Res. 1998 Nov 15;58(22):5216-20.

Abstract

P-selectin is a cell adhesion molecule that is sequestered in Weibel-Palade storage reservoirs within the vascular endothelium and alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / radiotherapy
  • Dose-Response Relationship, Radiation
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / radiation effects*
  • Glioma / blood supply*
  • Glioma / radiotherapy
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Nude
  • P-Selectin / metabolism*
  • Platelet Aggregation
  • Platelet Membrane Glycoproteins / immunology
  • Platelet Membrane Glycoproteins / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • P-Selectin
  • Platelet Membrane Glycoproteins