Inflammation and Cancer: A Comparative View

Morrison, Wallace B.

doi:10.1111/j.1939-1676.2011.00836.x

Cited by 92 publications

(87 citation statements)

References 130 publications

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“…20 Tumors associated with mutations, chromosomal translocations or mutations in tumor suppressor genes such as breast cancer susceptibility genes 1 and 2 undergo rapid tumorigenesis, 21 and such tumors are generally considered not to require inflammatory stimuli. However, our results in an osteosarcoma model indicate that inflammation is required for tumorigenesis even in mutation-induced tumors.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

et al. 2013

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“…22 In particular, several mutations in p53 have been associated with UGS-induced bladder cancer, for example, mutations in the coding region, codon 249, were identified in dysplasic and metaplasic lesions in the urinary bladder or frequently in invasive SCC of the bladder. 19,21,28,29 Here, we propose a pathway for the formation of these estrogen-like metabolites and describe key enzymes based on recent findings. [12][13][14][15][16] Emphasis is given to the tentative association between these metabolites, dysregulation of p53 and DNA damage in the target tissue-the urothelium of the urinary bladder-during UGS.…”

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confidence: 99%

The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer

et al. 2017

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Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasis-induced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these metabolites emphasizing their potential effects on the dysregulation of the tumor suppressor gene p53 expression during urogenital schistosomiasis. Enhanced understanding of these potential carcinogens may not only shed light on urogenital schistosomiasis-induced neoplasia of the bladder, but would also facilitate development of interventions and biomarkers for this and other infection-associated cancers at large.

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“…Although inflammation acts as an adaptive host defence against infection or injury and is primarily a selflimiting process, inadequate resolution of inflammatory responses often leads to various chronic ailments including cancer [36,37]. Sustained cellular injuries due to chronic trauma can cause inflammation, which may lead to carcinogenesis.…”

Section: Role Of Inflammation In Oral Carcinogenesismentioning

confidence: 99%