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Title: Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells

Abstract

Purpose: Radiotherapy resistance is a commonly encountered problem in cancer treatment. In this regard, stabilization of endothelial cells and release of angiogenic factors by cancer cells contribute to this problem. In this study, we used human lung adenocarcinoma (A549) cells to compare the effects of carbon ion and X-ray irradiation on the cells' angiogenic response. Methods and Materials: A549 cells were irradiated with biologically equivalent doses for cell survival of either carbon ions (linear energy transfer, 170 keV/{mu}m; energy of 9.8 MeV/u on target) or X-rays and injected with basement membrane matrix into BALB/c nu/nu mice to generate a plug, allowing quantification of angiogenesis by blood vessel enumeration. The expression of angiogenic factors (VEGF, PlGF, SDF-1, and SCF) was assessed at the mRNA and secreted protein levels by using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay. Signal transduction mediated by stem cell factor (SCF) was assessed by phosphorylation of its receptor c-Kit. For inhibition of SCF/c-Kit signaling, a specific SCF/c-Kit inhibitor (ISCK03) was used. Results: Irradiation of A549 cells with X-rays (6 Gy) but not carbon ions (2 Gy) resulted in a significant increase in blood vessel density (control, 20.71 {+-} 1.55; X-ray, 36.44 {+-} 3.44; carbon ion, 16.33 {+-}more » 1.03; number per microscopic field). Concordantly, irradiation with X-rays but not with carbon ions increased the expression of SCF and subsequently caused phosphorylation of c-Kit in endothelial cells. ISCK03 treatment of A549 cells irradiated with X-rays (6 Gy) resulted in a significant decrease in blood vessel density (X-ray, 36.44 {+-} 3.44; X-ray and ISCK03, 4.33 {+-} 0.71; number of microscopic field). These data indicate that irradiation of A549 cells with X-rays but not with carbon ions promotes angiogenesis. Conclusions: The present study provides evidence that SCF is an X-ray-induced mediator of angiogenesis in A549 cells, a phenomenon that could not be observed with carbon ion irradiation. Thus, in this model system evaluating angiogenesis, carbon ion irradiation may have a therapeutic advantage. This observation should be confirmed in orthotopic lung tumor models.« less

Authors:
 [1];  [2];  [1]; ;  [3]; ;  [1];  [3]; ; ;  [4];  [3];  [1];  [5];  [1]
  1. Department of Radiotherapy and Radiooncology, Philipps-University, Marburg (Germany)
  2. Department of Urology and Pediatric Urology, Philipps-University, Marburg (Germany)
  3. Department of Internal Medicine II/V, Justus-Liebig-University, Giessen (Germany)
  4. GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany)
  5. (Germany)
Publication Date:
OSTI Identifier:
21587657
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 80; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2011.03.033; PII: S0360-3016(11)00497-4; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANGIOGENESIS; BLOOD VESSELS; CARBON IONS; CARCINOMAS; ENZYMES; IRRADIATION; LUNGS; MESSENGER-RNA; PHOTONS; RADIOTHERAPY; STEM CELLS; X RADIATION; ANIMAL CELLS; BODY; BOSONS; CARDIOVASCULAR SYSTEM; CHARGED PARTICLES; DISEASES; ELECTROMAGNETIC RADIATION; ELEMENTARY PARTICLES; IONIZING RADIATIONS; IONS; MASSLESS PARTICLES; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; RADIATIONS; RADIOLOGY; RESPIRATORY SYSTEM; RNA; SOMATIC CELLS; THERAPY

Citation Formats

Kamlah, Florentine, E-mail: Kamlah@staff.uni-marburg.de, Haenze, Joerg, Arenz, Andrea, Seay, Ulrike, Hasan, Diya, Juricko, Janko, Bischoff, Birgit, Gottschald, Oana R., Fournier, Claudia, Taucher-Scholz, Gisela, Scholz, Michael, Seeger, Werner, Engenhart-Cabillic, Rita, Department of Radiotherapy, Justus-Liebig-University, Giessen, and Rose, Frank. Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells. United States: N. p., 2011. Web. doi:10.1016/j.ijrobp.2011.03.033.
Kamlah, Florentine, E-mail: Kamlah@staff.uni-marburg.de, Haenze, Joerg, Arenz, Andrea, Seay, Ulrike, Hasan, Diya, Juricko, Janko, Bischoff, Birgit, Gottschald, Oana R., Fournier, Claudia, Taucher-Scholz, Gisela, Scholz, Michael, Seeger, Werner, Engenhart-Cabillic, Rita, Department of Radiotherapy, Justus-Liebig-University, Giessen, & Rose, Frank. Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells. United States. doi:10.1016/j.ijrobp.2011.03.033.
Kamlah, Florentine, E-mail: Kamlah@staff.uni-marburg.de, Haenze, Joerg, Arenz, Andrea, Seay, Ulrike, Hasan, Diya, Juricko, Janko, Bischoff, Birgit, Gottschald, Oana R., Fournier, Claudia, Taucher-Scholz, Gisela, Scholz, Michael, Seeger, Werner, Engenhart-Cabillic, Rita, Department of Radiotherapy, Justus-Liebig-University, Giessen, and Rose, Frank. Mon . "Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells". United States. doi:10.1016/j.ijrobp.2011.03.033.
@article{osti_21587657,
title = {Comparison of the Effects of Carbon Ion and Photon Irradiation on the Angiogenic Response in Human Lung Adenocarcinoma Cells},
author = {Kamlah, Florentine, E-mail: Kamlah@staff.uni-marburg.de and Haenze, Joerg and Arenz, Andrea and Seay, Ulrike and Hasan, Diya and Juricko, Janko and Bischoff, Birgit and Gottschald, Oana R. and Fournier, Claudia and Taucher-Scholz, Gisela and Scholz, Michael and Seeger, Werner and Engenhart-Cabillic, Rita and Department of Radiotherapy, Justus-Liebig-University, Giessen and Rose, Frank},
abstractNote = {Purpose: Radiotherapy resistance is a commonly encountered problem in cancer treatment. In this regard, stabilization of endothelial cells and release of angiogenic factors by cancer cells contribute to this problem. In this study, we used human lung adenocarcinoma (A549) cells to compare the effects of carbon ion and X-ray irradiation on the cells' angiogenic response. Methods and Materials: A549 cells were irradiated with biologically equivalent doses for cell survival of either carbon ions (linear energy transfer, 170 keV/{mu}m; energy of 9.8 MeV/u on target) or X-rays and injected with basement membrane matrix into BALB/c nu/nu mice to generate a plug, allowing quantification of angiogenesis by blood vessel enumeration. The expression of angiogenic factors (VEGF, PlGF, SDF-1, and SCF) was assessed at the mRNA and secreted protein levels by using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay. Signal transduction mediated by stem cell factor (SCF) was assessed by phosphorylation of its receptor c-Kit. For inhibition of SCF/c-Kit signaling, a specific SCF/c-Kit inhibitor (ISCK03) was used. Results: Irradiation of A549 cells with X-rays (6 Gy) but not carbon ions (2 Gy) resulted in a significant increase in blood vessel density (control, 20.71 {+-} 1.55; X-ray, 36.44 {+-} 3.44; carbon ion, 16.33 {+-} 1.03; number per microscopic field). Concordantly, irradiation with X-rays but not with carbon ions increased the expression of SCF and subsequently caused phosphorylation of c-Kit in endothelial cells. ISCK03 treatment of A549 cells irradiated with X-rays (6 Gy) resulted in a significant decrease in blood vessel density (X-ray, 36.44 {+-} 3.44; X-ray and ISCK03, 4.33 {+-} 0.71; number of microscopic field). These data indicate that irradiation of A549 cells with X-rays but not with carbon ions promotes angiogenesis. Conclusions: The present study provides evidence that SCF is an X-ray-induced mediator of angiogenesis in A549 cells, a phenomenon that could not be observed with carbon ion irradiation. Thus, in this model system evaluating angiogenesis, carbon ion irradiation may have a therapeutic advantage. This observation should be confirmed in orthotopic lung tumor models.},
doi = {10.1016/j.ijrobp.2011.03.033},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 80,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 2011},
month = {Mon Aug 01 00:00:00 EDT 2011}
}