Sheng-Yung Fu1,2, Chun-Chieh Wang2,3,4, Fang-Hsin Chen2,3,4, Ching-Fang Yu2,4, Ji-Hong Hong5,3,4, Chi-Shiun Chiang6,7,8. 1. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, R.O.C. 2. Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital/Chang Gung University, Taoyuan, Taiwan, R.O.C. 3. Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, R.O.C. 4. Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan, R.O.C. 5. Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital/Chang Gung University, Taoyuan, Taiwan, R.O.C. cschiang@mx.nthu.edu.tw jihong@cgmh.org.tw. 6. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, R.O.C. cschiang@mx.nthu.edu.tw jihong@cgmh.org.tw. 7. Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C. 8. Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: The clinical response rate of prostate cancer to tyrosine kinase inhibitor (TKI) monotherapy is low. The mechanisms of resistance to TKI are unclear. This study aimed to examine if the tumor microenvironment (TME) is involved in the resistance. MATERIALS AND METHODS: The anti-vascular effect of Sutent was examined by immunofluorescent staining in TRAMP-C1 tumor. The percentage of CD11b+ population were analyzed by flow cytometry. The level of cytokines and chemokines were measured by multiplex immunoassay. RESULTS: The Sutent monotherapy caused 1.5 days of tumor growth delay, chronic hypoxia, and more mature vasculature. Sutent monotherapy increased the percentage of polymorphonuclear myeloid-derived suppressor cells (MDSCs) in peripheral blood. The evolved TME triggered the re-distribution of myeloid cells in chronically hypoxic areas. The multiplex immunoassay indicated higher levels of several cytokines and chemokines both in tumors and the blood. CONCLUSION: Sunitinib treatment induced a distinct tumor microenvironment that impaired the efficient reduction of MDSCs by TKI. Copyright
BACKGROUND/AIM: The clinical response rate of prostate cancer to tyrosine kinase inhibitor (TKI) monotherapy is low. The mechanisms of resistance to TKI are unclear. This study aimed to examine if the tumor microenvironment (TME) is involved in the resistance. MATERIALS AND METHODS: The anti-vascular effect of Sutent was examined by immunofluorescent staining in TRAMP-C1 tumor. The percentage of CD11b+ population were analyzed by flow cytometry. The level of cytokines and chemokines were measured by multiplex immunoassay. RESULTS: The Sutent monotherapy caused 1.5 days of tumor growth delay, chronic hypoxia, and more mature vasculature. Sutent monotherapy increased the percentage of polymorphonuclear myeloid-derived suppressor cells (MDSCs) in peripheral blood. The evolved TME triggered the re-distribution of myeloid cells in chronically hypoxic areas. The multiplex immunoassay indicated higher levels of several cytokines and chemokines both in tumors and the blood. CONCLUSION:Sunitinib treatment induced a distinct tumor microenvironment that impaired the efficient reduction of MDSCs by TKI. Copyright
Authors: Junko Ozao-Choy; Ge Ma; Johnny Kao; George X Wang; Marcia Meseck; Max Sung; Myron Schwartz; Celia M Divino; Ping-Ying Pan; Shu-Hsia Chen Journal: Cancer Res Date: 2009-03-10 Impact factor: 12.701