TNFR-1 on tumor cells contributes to the sensitivity of fibrosarcoma to chemotherapy.
10.1007/s13238-013-3008-y
- Author:
Jingjing DENG
1
,
2
;
Xiaopu ZHAO
;
Lijie RONG
;
Xiao LI
;
Xiaoman LIU
;
Zhihai QIN
Author Information
1. Key Laboratory of Protein and Peptide Pharmaceuticals
2. Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Down-Regulation;
drug effects;
Fibrosarcoma;
drug therapy;
genetics;
pathology;
Gene Expression Regulation, Neoplastic;
drug effects;
Humans;
Melphalan;
administration & dosage;
Mice;
Molecular Targeted Therapy;
Receptors, Tumor Necrosis Factor, Type I;
genetics;
Signal Transduction;
drug effects;
Vascular Endothelial Growth Factor A;
biosynthesis
- From:
Protein & Cell
2013;4(5):393-401
- CountryChina
- Language:English
-
Abstract:
Impaired tumor necrosis factor receptor-1 (TNFR-1) signaling has been found in some malignant tumors with poor prognosis. However, the exact role of TNFR-1 signaling in fibrosarcoma remains unclear. Here, we explored the question by comparing the growth of TNFR-1 deficient (Tnfr1 (-)) and TNFR-1 competent (Tnfr1 (+)) fibrosarcoma FB61 cells (FB61-m and FB61-R1) in mice. TNFR-1 expression on fibrosarcoma cells delayed their growth in vivo but not in vitro. Moreover, reduced FB61-R1 tumor growth was also obtained in TNFR-1 knockout mice. The mechanism relies mainly on the TNFR-1-mediated downregulation of vascular endothelial growth factor (VEGF) production by tumor cells. Importantly, treatment of FB61-m tumors with melphalan resulted in a short delay of tumor growth, followed by a quick remission. However, when FB61-R1 tumors were treated with melphalan, tumor growth was similarly delayed at first and then completely rejected. Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fibrosarcoma, and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.
