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COX2 confers bone marrow stromal cells to promoting TNFα/TNFR1ß-mediated myeloma cell growth and adhesion.
Kuang, Chunmei; Zhu, Yinghong; Guan, Yongjun; Xia, Jiliang; Ouyang, Jian; Liu, Guizhu; Hao, Mu; Liu, Jiabin; Guo, Jiaojiao; Zhang, Wenxia; Feng, Xiangling; Li, Xin; Zhang, Jingyu; Wu, Xuan; Xu, Hang; Li, Guancheng; Xie, Lu; Fan, Songqing; Qiu, Lugui; Zhou, Wen.
  • Kuang C; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Zhu Y; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Guan Y; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Xia J; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Ouyang J; Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, 201203, China.
  • Liu G; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, 200030, China.
  • Hao M; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300020, China.
  • Liu J; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Guo J; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Zhang W; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300020, China.
  • Feng X; Xiang Ya School of Public Health, Central South University, Changsha, 410078, China.
  • Li X; Department of hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
  • Zhang J; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Wu X; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Xu H; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Li G; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
  • Xie L; Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, 201203, China.
  • Fan S; Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Qiu L; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300020, China.
  • Zhou W; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Department of Hematology, Xiangya Hospital; Cancer Research Institute, School of Basic Medical Sciences, Central South University, Ch
Cell Oncol (Dordr) ; 44(3): 643-659, 2021 Jun.
Article en En | MEDLINE | ID: mdl-33646559
PURPOSE: Bone marrow stromal cells (BMSCs) have been implicated in multiple myeloma (MM) progression. However, the underlying mechanisms remain largely elusive. Therefore, we aimed to explore key factors in BMSCs that contribute to MM development. METHODS: RNA-sequencing was used to perform gene expression profiling in BMSCs. Enzyme-linked immunosorbent assays (ELISAs) were performed to determine the concentrations of PGE2 and TNFα in sera and conditioned media (CM). Western blotting, qRT-PCR and IHC were used to examine the expression of cyclooxygenase 2 (COX2) in BMSCs and to analyze the regulation of TNFα by COX2. Cell growth and adhesion assays were employed to explore the function of COX2 in vitro. A 5T33MMvt-KaLwRij mouse model was used to study the effects of COX2 inhibition in vivo. RESULTS: COX2 was found to be upregulated in MM patient-derived BMSCs and to play a critical role in BMSC-induced MM cell proliferation and adhesion. Administration of PGE2 to CM derived from BMSCs promoted MM cell proliferation and adhesion. Conversely, inhibition of COX2 in BMSCs greatly compromised BMSC-induced MM cell proliferation and adhesion. PCR array-based analysis of inflammatory cytokines indicated that COX2 upregulates the expression of TNFα. Subsequent rescue assays showed that an anti-TNFα monoclonal antibody could antagonize COX2-mediated MM cell proliferation and adhesion. Administration of NS398, a specific COX2 inhibitor, inhibited in vivo tumor growth and improved the survival of 5TMM mice. CONCLUSIONS: Our results indicate that COX2 contributes to BMSC-induced MM proliferation and adhesion by increasing the secretion of PGE2 and TNFα. Targeting COX2 in BMSCs may serve as a potential therapeutic approach of treating MM.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Factor de Necrosis Tumoral alfa / Receptores Tipo I de Factores de Necrosis Tumoral / Ciclooxigenasa 2 / Células Madre Mesenquimatosas / Mieloma Múltiple Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2021 Tipo del documento: Article
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Factor de Necrosis Tumoral alfa / Receptores Tipo I de Factores de Necrosis Tumoral / Ciclooxigenasa 2 / Células Madre Mesenquimatosas / Mieloma Múltiple Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2021 Tipo del documento: Article