Interleukin-6 and melanoma

Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

doi:10.1097/cmr.0b013e3283543d72

Cited by 71 publications

(73 citation statements)

References 70 publications

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“…23 Interestingly, we found that inhibition of osteoblastic differentiation by TNFa or IL-1 through ERK was required for AX cell tumorigenesis through the maintenance of an undifferentiated state. Although IL-6 is an inflammatory cytokine implicated in tumorigenesis of various cancers, 15,16 IL-6 was not required for tumor development in this osteosarcoma model. Therefore, inflammatory cytokines, such as TNFa or IL-1 or ERKs could serve as therapeutic targets for such mutation-induced tumors.…”

Section: Discussionmentioning

confidence: 82%

“…osteosarcoma patients, 9 and IL-6 is implicated in the development of various tumors. [15][16][17] Thus, we transplanted AX cells into IL-6-deficient or wild-type mice in order to compare mouse survival rates (Figure 1b). However, survival rates of AX cell-bearing mice of either genotype were comparable (Figure 1b), suggesting that IL-6 does not function in AX cell tumorigenesis in vivo.…”

Section: Introductionmentioning

confidence: 99%

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TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state

et al. 2013

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Chronic inflammation is frequently associated with tumorigenesis in elderly people. By contrast, young people without chronic inflammation often develop tumors considered independent of chronic inflammation but driven instead by mutations. Thus, whether inflammation has a significant role in tumor progression in tumors driven by mutations remains largely unknown. Here we show that TNFa is required for the tumorigenesis of osteosarcoma, the most common tumor in children and adolescents. We show that transplantation of AX osteosarcoma cells, which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wildtype mice promotes lethal tumorigenesis accompanied by ectopic bone formation and multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis was completely abrogated in TNFa-deficient mice. AX cells have the capacity to undergo osteoblastic differentiation; however, that activity was significantly inhibited by TNFa treatment, suggesting that TNFa maintains AX cells in an undifferentiated state. TNFa inhibition of AX cell osteoblastic differentiation occurred through ERK activation, and a pharmacological TNFa inhibitor effectively inhibited both AX cell tumorigenesis and increased osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal tumorigenesis of AX cells was also abrogated in IL-1a/IL-1b doubly deficient mice. We found that both TNFa and IL-1 maintained AX cells in an undifferentiated state via ERK activation. Thus, inflammatory cytokines are required to promote tumorigenesis even in mutation-induced tumors, and TNFa/IL-1 and ERK may represent therapeutic targets for osteosarcoma.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state

et al. 2013

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“…In addition, it promoted tumor growth and invasion, which is consistent with previous studies. 22, 23, 24 Increased serum levels of IL-6 were an independent prognostic biomarker of shorter overall survival in metastatic melanoma patients. 25 Therefore, the reduced miR-98 levels in these patients will likely result in a concomitant increase in IL-6 levels and poorer prognosis.…”

Section: Discussionmentioning

confidence: 97%

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

Qiao

et al. 2014

Exp Mol Med

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Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.

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“…We wished to examine the gene expression of key cytokines and/or their receptors associated with B16/F10 tumor growth in aged tissues in vivo and aged 3D collagen in vitro. We chose four genes that regulate growth pathways, such as JAK-STAT, and are implicated in melanoma tumor promotion and progression: growth hormone receptor (GHR) (Lincoln et al 1999), interleukin-10 receptor beta (IL-10Rβ) (Seftor et al 2002), interleukin-4 receptor alpha (IL-4Rα) (Obiri et al 1994), and interleukin-6 (IL-6) (Colombo et al 1992; Hoejberg et al 2012). Six tumors grown in vivo were removed and a portion immediately processed for RNA extraction using Trizol (Ambion, Grand Island, NY).…”

Section: Methods Results and Discussionmentioning

confidence: 99%

B16/F10 tumors in aged 3D collagen in vitro simulate tumor growth and gene expression in aged mice in vivo

Bentov

Damodarasamy

Plymate

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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Although the incidence of cancer rises with age, tumor growth is often slowed in older hosts. The B16/F10 melanoma cell line is commonly used in murine models of age-related tumor growth suppression. We wished to determine if the growth pattern and gene expression of B16/10 tumors grown in aged mice could be simulated in 3D collagen matrices derived from aged mice. Outcome measures were tumor size in vitro and gene expression of the key growth regulatory molecules: growth hormone receptor (GHR), IL-10Rβ, IL-4Rα, and IL-6. B16/F10 tumors were grown in 20–25-mo-old C57/BL6 male mice. Tumor sizes ranged from 30 to 4,910 mg in vivo. Tumors from a subset of mice were removed after euthanasia, and equivalent amounts of each tumor were placed in aged 3D collagen and grown for 5 d. Tumor sizes in aged 3D collagen correlated highly with their original tumor size in vivo. Gene expression changes noted in vivo were also maintained during tumor growth in aged 3D collagen in vitro. The relative expression of GHR was increased, IL-10Rβ was unchanged, and IL-4Rα and IL-6 were decreased in the larger tumors relative to the smaller tumors in vitro, in a pattern similar to that noted in vivo. We propose that 3D matrices from aged mice provide an in vitro model of tumor growth that correlates highly with tumor size and expression of key regulatory molecules in vivo.

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Interleukin-6 and melanoma

Cited by 71 publications

References 70 publications

TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state

TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

B16/F10 tumors in aged 3D collagen in vitro simulate tumor growth and gene expression in aged mice in vivo

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