摘要
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 fi brosarcoma 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 T NFR-1 knockout mice.The mechanism relies mainly on the TNFR-1-mediated down-regulation 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 r emission.However,when FB61-R1 tumors were treated with melphalan,tumor growth was similarly delayed at fi rst and then completely rejected.Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fi brosarcoma,and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.
基金
supported by the Ministry of Science and Technology of China(Grant No.2012CB917103)
National Natural Science Foundation of China(Grant Nos.81030049 and 91229203).
