|Author||Rodriguez-Ruiz, María E. ♦ Garasa, Saray ♦ Rodriguez, Inmaculada ♦ Solorzano, Jose Luis ♦ Barbes, Benigno ♦ Yanguas, Alba ♦ Teijeira, Alvaro ♦ Etxeberria, Iñaki ♦ Aristu, José Javier ♦ Halin, Cornelia ♦ Melero, Ignacio ♦ Rouzaut, Ana|
|Source||United States Department of Energy Office of Scientific and Technical Information|
|Subject Keyword||RADIOLOGY AND NUCLEAR MEDICINE ♦ ADHESION ♦ GY RANGE 10-100 ♦ IRRADIATION ♦ LINEAR ACCELERATORS ♦ NEOPLASMS ♦ PLANT TISSUES ♦ RADIATION DOSES ♦ RADIOTHERAPY ♦ TIME DEPENDENCE|
|Abstract||Purpose/Objectives: The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Materials/Methods: Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. Results: We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Conclusion: Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to immunotherapy.|
|Learning Resource Type||Article|
|Publisher Place||United States|
|Journal||International Journal of Radiation Oncology, Biology and Physics|
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