Understanding melanoma evolution during disease progression.

Dr Mark Shackleton et.al.

Melanoma is a cancer arising from cells in the body called melanocytes. As normal melanocytes mature they produce the pigment, melanin, which can determine features such as  hair, eye and skin colour. When they  become cancerous, some melanomas continue to produce melanin, but other melanomas curiously do not. We sought to determine whether melanin production has any impact on the way that melanomas grow, spread and respond to treatment. Through MMP we obtained archived tumour material from consenting patients with stage 1/ 2 (primary) or stage 3/4 (metastatic) melanoma, and looked for melanin. Significantly, we found that metastatic melanomas were over 5-times more likely to be devoid of melanin. Moreover, we discovered that many melanomas produce melanin initially but lose it as they progress. To study this further we established laboratory models of human melanoma and observed that melanoma cells that cease to produce melanin out-grow melanin-producing cells in the same tumour. To understand why some melanoma cells act differently from others, we extracted proteins (molecules within cells that control their behaviour) from melanoma cells that either do or do not produce melanin. We discovered that melanin-devoid cells have increased levels of two important proteins called UFO and c-Myc. Significantly, UFO has been found to be involved in resistance to some anti-melanoma drugs, and c-Myc is known to promote tumour cell growth. Therefore, we propose that in many melanomas loss of melanin may promote growth and drug resistance, and that targeting proteins increased in melanin-devoid tumours may  lead to more effective anti-melanoma therapies.