ArticleJournal of the National Cancer Institute2016
Role of Myeloma-Derived MIF in Myeloma Cell Adhesion to Bone Marrow and Chemotherapy Response.
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Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
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35 citing papers in PubMed, 57 citations in OpenAlex.
- MIF tautomerase inhibitor 4-IPP alleviates HFD-induced obesity by restoring CD137-mediated browning of white adipocytes in mice.Acta pharmacologica Sinica · 2026Article
- Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions.bioRxiv : the preprint server for biology · 2026Article
- The role of KPNA3 in multiple myeloma: implications for targeting nuclear import.Apoptosis : an international journal on programmed cell death · 2026Article
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- Immunophenotypic changes in the tumor and tumor microenvironment during progression to multiple myeloma.PLoS genetics · 2025Article
- Macrophage Migration Inhibitory Factor (MIF) Upregulates CXCR7 and Contributes to Chemotherapy Resistance in Colorectal Cancer.Cell biochemistry and biophysics · 2024Article
- Implications of PD-L1 expression on the immune microenvironment in HER2-positive gastric cancer.Molecular cancer · 2024Article
- A novel class of inhibitors that disrupts the stability of integrin heterodimers identified by CRISPR-tiling-instructed genetic screens.Nature structural & molecular biology · 2024Article
- Accounting for Nonhealth and Future Costs in Cost-Effectiveness Analysis: Distributional Impacts of a US Cancer Prevention Strategy.PharmacoEconomics · 2023Article
- Simultaneously Targeting Two Coupled Signalling Molecules in the Mesenchymal Stem Cell Support Efficiently Sensitises the Multiple Myeloma Cell Line H929 to Bortezomib.International journal of molecular sciences · 2023Article
- Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?Pharmaceuticals (Basel, Switzerland) · 2023Review
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- ISG20L2 suppresses bortezomib antimyeloma activity by attenuating bortezomib binding to PSMB5.JCI insight · 2022Article
- Highly expressed genes in multiple myeloma cells - what can they tell us about the disease?European journal of haematology · 2022Article
- MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment.BMC cancer · 2022Article
- Recent Advances on the Role of ATGL in Cancer.Frontiers in oncology · 2022Review
- Overcoming tumor resistance mechanisms in CAR-NK cell therapy.Frontiers in immunology · 2022Review
- Effect of crosstalk among conspirators in tumor microenvironment on niche metastasis of gastric cancer.American journal of cancer research · 2022Review
- ALCAM-EGFR interaction regulates myelomagenesis.Blood advances · 2021Article
- The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers.Cancers · 2021Review
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Authors and funding
14 authors at 6 institutions in 2 countries.
Yuhuan ZhengAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Qiang WangAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Tianshu LiAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Jianfei QianAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Yong LuAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Yi LiAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Enguang BiAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Frederic ReuAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Yu QinAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Judy DrazbaAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Eric HsiAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Jing YangAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Zhen CaiAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Qing YiAffiliations of authors: Department of Hematology and State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, West China Hospital, China (YZ); Department of Cancer Biology (YZ, QW, TL, JQ, YLu, YLi, EB, QY), Taussig Cancer Center (FR), Imaging Core Facility, Lerner Research Institute (JD), and Department of Pathology and Laboratory Medicine Institute (EH), Cleveland Clinic, Cleveland, OH; Department of Hematology, Zhejiang University, China (YLi, ZC); Department of Internal Medicine, Weiss Memory Hospital, Chicago, IL (YQ); Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX (JY).
Weiss Memorial Hospital · USCerner (United States) · USState Key Laboratory of BiotherapyZhejiang University · CNCleveland Clinic · USSichuan University · CN
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MTargeting Plasmacytoid Dendritic Cells to Treat Human MyelomaR01CA163881 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YI, QING · 2012 to 2016
$2.0MRole of integrin VLA-6 in suppression of bone formation in myelomaR01CA193362 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YANG, JING · 2016 to 2020
$1.8MC-reactive protein promotes myeloma cell-mediated bone destructionR01CA138398 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YI, QING · 2010 to 2014
$1.6MTargeting surface b2M for myeloma and bone therapyR01CA138402 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YI, QING · 2009 to 2013
$1.3MNCI NIH HHS R01 CA138398NCI NIH HHS R01 CA138402NCI NIH HHS R01 CA163881NCI NIH HHS R01 CA193362
Abstract
backgroundMultiple myeloma (MM) remains an incurable cancer characterized by accumulation of malignant plasma cells in the bone marrow (BM). The mechanism underlying MM homing to BM is poorly elucidated.
methodsThe clinical significance of migration inhibitory factor (MIF) expression was examined by analyzing six independent gene expression profile databases of primary MM cells using the Student's t test and Kaplan-Meier test. Enzyme-linked immunosorbent assay was used to examine MIF expression. In vivo bioluminescent imaging was used to determine MM cell localization and treatment efficacy in human MM xenograft mouse models, with three to four mice per group. MM cell attachment to BM stromal cells (BMSCs) was monitored by cell adhesion assay. MIF regulation of the expression of adhesion molecules was determined by chromatin immunoprecipitation (ChIP) assay. Statistical tests were two-sided.
resultsHigh levels of MIF were detected in MM BM (MIF level in BM plasma: healthy = 10.72 ± 5.788 ng/mL, n = 5; MM = 1811 ± 248.7 ng/mL, n = 10; P < .001) and associated with poor survival of patients (Kaplan-Meier test for MM OS: 87 MIF(high) patients, 86 MIF(low) patients, P = .02). Knocking down MIF impaired MM cell adhesion to BMSCs in vitro and led to formation of extramedullary tumors in SCID mice. MIF acted through surface receptor CXCR4 and adaptor COPS5 to regulate the expression of adhesion molecules ALCAM, ITGAV, and ITGB5 on MM cells. More importantly, MIF-deficient MM cells were sensitive to chemotherapy in vitro when cocultured with BMSCs and in vivo. MIF inhibitor 4-IPP sensitized MM cells to chemotherapy.
conclusionsMIF is an important player and a novel therapeutic target in MM. Inhibiting MIF activity will sensitize MM cells to chemotherapy.
Indexed as
Activated-Leukocyte Cell Adhesion MoleculeAnimalsAntigens, Differentiation, B-LymphocyteAntineoplastic Agents, AlkylatingApoptosisAutocrine CommunicationBone MarrowBortezomibCell AdhesionCell Line, TumorChemotaxisCoculture TechniquesCOP9 Signalosome ComplexDrug Resistance, NeoplasmFemaleGene Expression4-iodo-6-phenylpyrimidineActivated-Leukocyte Cell Adhesion MoleculeAntigens, Differentiation, B-LymphocyteAntineoplastic Agents, AlkylatingBortezomibCOP9 Signalosome ComplexCOPS5 protein, humanHistocompatibility Antigens Class IIIntracellular Signaling Peptides and ProteinsIntramolecular Oxidoreductasesinvariant chainMacrophage Migration-Inhibitory FactorsMelphalanMIF protein, humanPeptide HydrolasesPyrimidinesReceptors, CXCR4RNA, Messenger
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