title: TNFR-1 on tumor cells contributes to the sensitivity of fibrosarcoma to chemotherapy.
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.
authors: Key Laboratory of Protein and Peptide Pharmaceuticals; Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Jingjing
authors: J
authors: Deng
authors: Xiaopu
authors: X
authors: Zhao
authors: Lijie
authors: L
authors: Rong
authors: Xiao
authors: X
authors: Li
authors: Xiaoman
authors: X
authors: Liu
authors: Zhihai
authors: Z
authors: Qin
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage*; D051379:Mice; D058990:Molecular Targeted Therapy; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D008558:Melphalan
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