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Altered Biological Potential and Radioresponse of Murine Tumors in Different Microenvironments

 Ik Jae Lee  ;  Eun Jeong Lee  ;  Hyojin Park  ;  Wonwoo Kim  ;  Sang-Jun Ha  ;  You Keun Shin  ;  Jinsil Seong 
 CANCER RESEARCH AND TREATMENT, Vol.48(2) : 727-737, 2016 
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Animals ; Cell Line, Tumor ; Cyclooxygenase 2/metabolism ; Interleukin-6/blood ; Liver Neoplasms/immunology ; Liver Neoplasms/pathology* ; Liver Neoplasms/radiotherapy* ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/radiation effects ; Male ; Mice ; Mice, Inbred C3H ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/radiation effects ; Neoplasm Transplantation ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/radiation effects ; Transforming Growth Factor beta1/metabolism ; Tumor Microenvironment*/radiation effects ; Vascular Endothelial Growth Factor A/metabolism
Hepatocarcinoma ; Radiation ; Tumor microenvironment
PURPOSE: This study was conducted to evaluate the biological features of murine hepatocarcinoma according to different tumor microenvironmental models and to determine the change in molecular and immunologic responses after radiation. MATERIALS AND METHODS: Tumor models were established in the liver (orthotopic) and thigh (heterotopic) of male C3H/HeN mice. Tumor growth and lung metastasis were assessed in these models. To evaluate the radiation effect, the tumors were irradiated with 10 Gy. Factors associated with tumor microenvironment including vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), transforming growth factor beta1 (TGF-β1), CD31, and serum interleukin-6 (IL-6) were evaluated. Tumor-infiltrating regulatory immune cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) were also analyzed. RESULTS: A higher number of lung metastases were observed in the orthotopic tumor model than in the heterotopic tumor model. VEGF, CD31, COX-2, and TGF-β1 expression was more prominent in the orthotopic tumor model than in the heterotopic tumor model. Expression of the angiogenic factor VEGF and key regulatory molecules (TGF-β1 and COX-2) decreased following radiation in the orthotopic tumor model, while the serum IL-6 level increased after radiation. In the orthotopic tumor model, the number of both Tregs and MDSCs in the tumor burden decreased after radiation. CONCLUSION: The orthotopic tumor model showed higher metastatic potential and more aggressive molecular features than the heterotopic tumor model. These findings suggest that the orthotopic tumor mouse model may be more reflective of the tumor microenvironment and suitable for use in the translational research of radiation treatment.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Lee, Eun Jung(이은정)
Lee, Ik Jae(이익재) ORCID logo https://orcid.org/0000-0001-7165-3373
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