Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium
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- 作者：Marí ; a E. Rodriguez-Ruiz ; MD ; PhD&lowast ; ; &dagger ; ; mrruiz@unav.es ; Saray Garasa ; TS&lowast ; ; Inmaculada Rodriguez ; BS&lowast ; ; Jose Luis Solorzano ; MD ; PhD&dagger ; ; Benigno Barbes ; MD ; PhD&dagger ; ; Alba Yanguas ; BS&lowast ; ; § ; ; Alvaro Teijeira ; PhD&lowast ; ; Iñ ; aki Etxeberria ; BS&lowast ; ; José ; Javier Aristu ; MD ; PhD&dagger ; ; Cornelia Halin ; PhD&Dagger ; ; Ignacio Melero ; MD ; PhD&lowast ; ; &dagger ; ; Ana Rouzaut ; PhD&lowast ; ; § ;
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2017
- 出版时间：1 February 2017
- 年：2017
- 卷：97
- 期：2
- 页码：389-400
- 全文大小：3373 K
- 卷排序：97
文摘
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/MethodsConfluent 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.ResultsWe 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.ConclusionOur 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.