Osteoblasts contribute to a protective niche that supports melanoma cell proliferation and survival

• DOI: 10.1111/pcmr.12812
• Publication Date: 2019-07-19T18:12:54Z
• Authors: Jennifer Ferguson; Daniel J. Wilcock; Sophie McEntegart; Andrew P. Badrock; Mitch Levesque; Reinhard Dummer; Claudia Wellbrock; Michael P. Smith
• Keywords: Microphthalmia-associated transcription factor

Melanoma is the deadliest form of skin cancer; a primary driver this high level morbidity propensity melanoma cells to metastasize. When malignant tumours develop distant metastatic lesions new local tissue niche known impact on biology cancer cells. However, little about how different sites frontline targeted therapies. Intriguingly, bone have significantly lower response BRAF or MEK inhibitor Here, we investigated cellular can support by stimulating growth and survival via paracrine signalling between osteoblasts enhance differentiation leading increased production secreted ligands, including RANKL. Differentiated in turn cell proliferation secretion RANKL that elevates levels transcription factor MITF, even presence inhibitor. By blocking signalling, either neutralizing antibodies, genetic alterations receptor SPD304, advantage provided could be overcome.