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dc.contributor.authorFerguson, J
dc.contributor.authorWilcock, DJ
dc.contributor.authorMcEntegart, S
dc.contributor.authorBadrock, AP
dc.contributor.authorLevesque, M
dc.contributor.authorDummer, R
dc.contributor.authorWellbrock, Claudia
dc.contributor.authorSmith, M P
dc.date.accessioned2019-10-04T09:48:32Z
dc.date.available2019-10-04T09:48:32Z
dc.date.issued2019en
dc.identifier.citationFerguson J, Wilcock DJ, McEntegart S, Badrock AP, Levesque M, Dummer R, et al. Osteoblasts contribute to a protective niche that supports melanoma cell proliferation and survival. Pigment Cell Melanoma Res. 2019 Jul 19.en
dc.identifier.pmid31323160en
dc.identifier.doi10.1111/pcmr.12812en
dc.identifier.urihttp://hdl.handle.net/10541/622159
dc.description.abstractMelanoma is the deadliest form of skin cancer; a primary driver of this high level of morbidity is the propensity of melanoma cells to metastasize. When malignant tumours develop distant metastatic lesions the new local tissue niche is known to impact on the biology of the cancer cells. However, little is known about how different metastatic tissue sites impact on frontline targeted therapies. Intriguingly, melanoma bone lesions have significantly lower response to BRAF or MEK inhibitor therapies. Here, we have investigated how the cellular niche of the bone can support melanoma cells by stimulating growth and survival via paracrine signalling between osteoblasts and cancer cells. Melanoma cells can enhance the differentiation of osteoblasts leading to increased production of secreted ligands, including RANKL. Differentiated osteoblasts in turn can support melanoma cell proliferation and survival via the secretion of RANKL that elevates the levels of the transcription factor MITF, even in the presence of BRAF inhibitor. By blocking RANKL signalling, either via neutralizing antibodies, genetic alterations or the RANKL receptor inhibitor SPD304, the survival advantage provided by osteoblasts could be overcome.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1111/pcmr.12812en
dc.titleOsteoblasts contribute to a protective niche that supports melanoma cell proliferation and survivalen
dc.typeArticleen
dc.contributor.departmentManchester Cancer Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchesteren
dc.identifier.journalPigment Cell & Melanoma Researchen
dc.description.noteen]
refterms.dateFOA2019-10-08T20:40:51Z


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