Macrophage migration inhibitory factor increases cell motility and up‐regulates αvβ3 integrin in human chondrosarcoma cells

Lee, Chun-Yi; Su, Mei-Ju; Huang, Chun‐Yin; Chen, Mengyi; Hsu, Horng‐Chaung; Lin, Ching‐Yuang; Tang, Chih-Hsin

doi:10.1002/jcb.24027

Cited by 25 publications

(17 citation statements)

References 40 publications

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“…Various studies have suggested that MIF can influence the cellular biological response by inducing the nuclear factor-kappa B (NF- kB), Erk1/2 and activating protein-1 (AP-1) signaling pathways, or by binding CD74/CD44 receptor complex 17. MIF-induced activation of PI3K/Akt pathway and α v β 3 integrin has been also demonstrated to involve in the development and progression of breast, gastric cancer and chondrosarcoma 18-20. Recently, tumor-derived MIF has been shown to closely correlate with tumor aggressiveness and metastatic potential.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of Macrophage Migration Inhibitory Factor and DJ-1 contribute to Cell Invasion and Metastasis of Nasopharyngeal Carcinoma

Pei¹,

Wu²,

Li³

et al. 2014

Int. J. Med. Sci.

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Background and aim: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism.Methods: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting.Results: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion.Conclusions: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

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Section: Introductionmentioning

confidence: 99%

Increased Expression of Macrophage Migration Inhibitory Factor and DJ-1 contribute to Cell Invasion and Metastasis of Nasopharyngeal Carcinoma

Pei¹,

Wu²,

Li³

et al. 2014

Int. J. Med. Sci.

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“…In addition, they have been implicated in the metastasis of chondrosarcomas and lung, breast, bladder, and colon cancers [10–13]. The α v β 3 integrin, in particular, has been reported in chondrosarcoma progression, with effects on angiogenesis, survival, and invasion [14, 15]. In vitro studies have also found that the α v β 3 integrin facilitated chondrosarcoma migration and invasion through several ECM substrates and transendothelial migration [16].…”

Section: Introductionmentioning

confidence: 99%

Berberine Reduces the Metastasis of Chondrosarcoma by Modulating theαvβ3 Integrin and the PKCδ, c-Src, and AP-1 Signaling Pathways

Tan

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis, especially to the lungs. Patients diagnosed with chondrosarcoma have poor prognosis. Berberine, an active component of the Ranunculaceae and Papaveraceae families of plant, has been proven to induce tumor apoptosis and to prevent the metastasis of cancer cells. However, the effects of berberine in human chondrosarcoma are largely unknown. In this study, we found that berberine did not induce cell apoptosis in human primary chondrocytes and chondrosarcoma cells. However, at noncytotoxic concentrations, berberine reduced the migration and invasion of chondrosarcoma cancer cells. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. We also found that incubation of chondrosarcoma cells with berberine reduced mRNA transcription for, and cell surface expression of, the αvβ3 integrin, with additional inhibitory effects on PKCδ, c-Src, and NF-κB activation. Thus, berberine may be a novel antimetastasis agent for the treatment of metastatic chondrosarcoma.

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“…Rheumatoid synovial fibroblasts show enhanced cellular adhesiveness, which may reflect the ability of CD44 to form a cocomplex with α ν β 3 integrin (47). MIF up-regulates α ν β 3 integrin expression in chondrosarcomas (48,49), and the addition of MIF to RA-FLSs also increased α ν β 3 integrin expression together with cell adhesiveness (Fig. 6 A and B).…”

Section: Mif-cd74/cd44 Axis Promotes Synovial Fibroblast Adhesion Andmentioning

confidence: 92%

MIFallele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis

Yoo

Leng

Kim

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Fibroblast-like synoviocytes mediate joint destruction in rheumatoid arthritis and exhibit sustained proinflammatory and invasive properties. CD44 is a polymorphic transmembrane protein with defined roles in matrix interaction and tumor invasion that is also a signaling coreceptor for macrophage migration inhibitory factor (MIF), which engages cell surface CD74. High-expression MIF alleles (rs5844572) are associated with rheumatoid joint erosion, but whether MIF signaling through the CD74/CD44 receptor complex promotes upstream autoimmune responses or contributes directly to synovial joint destruction is unknown. We report here the functional regulation of CD44 by an autocrine pathway in synovial fibroblasts that is driven by high-expression MIF alleles to up-regulate an inflammatory and invasive phenotype. MIF increases CD44 expression, promotes its recruitment into a functional signal transduction complex, and stimulates alternative exon splicing, leading to expression of the CD44v3-v6 isoforms associated with oncogenic invasion. CD44 recruitment into the MIF receptor complex, downstream MAPK and RhoA signaling, and invasive phenotype require MIF and CD74 and are reduced by MIF pathway antagonists. These data support a functional role for high-MIF expression alleles and the two-component CD74/CD44 MIF receptor in rheumatoid arthritis and suggest that pharmacologic inhibition of this pathway may offer a specific means to interfere with progressive joint destruction.immunogenetics | autoimmunity | MIF | CD44 | CD74

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Macrophage migration inhibitory factor increases cell motility and up‐regulates αvβ3 integrin in human chondrosarcoma cells

Cited by 25 publications

References 40 publications

Increased Expression of Macrophage Migration Inhibitory Factor and DJ-1 contribute to Cell Invasion and Metastasis of Nasopharyngeal Carcinoma

Increased Expression of Macrophage Migration Inhibitory Factor and DJ-1 contribute to Cell Invasion and Metastasis of Nasopharyngeal Carcinoma

Berberine Reduces the Metastasis of Chondrosarcoma by Modulating theαvβ3 Integrin and the PKCδ, c-Src, and AP-1 Signaling Pathways

MIFallele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis

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