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J Clin Oncol. Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent.

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The role of hypoxia-inducible factors in cancer. Cell Mol Life Sci. Melanoblasts, undifferentiated cells, reach not only the skin and hair follicle, but also the eyes, meninges, heart and cochlea, where they transform into melanocytes. The synthesis and storing of melanin takes place in the cellular organelles specific to melanocytes, called melanosomes.

Melanosomes have a different structure and function, according to the synthetized melanic pigment. While in the perinuclear region of melanocytes, melanosomes are immature and non-pigmented. As they migrate to dendrites, they undergo a series of conformational changes and become mature, pigmented and electron-opaque Melanosomes are present in black-skin people, melanocytes are larger, more elongated as well as numerous, and keratinocytes degrade more slowly.

In the epidermis, melanocytes are inserted into the keratinocytes due to their long and fine prolongations.

Melanin synthesis pathway -- Phenylalanine Metabolism -- Part-2 -- Biochemistry

A melanocyte is surrounded by 36 keratinocytes with which it forms the epidermal unit, whose activity is paracrine regulated. On the one hand, the synthesized quantity of melanic pigments at the melanocyte level is influenced stimulated or inhibited by a series of factors secreted by the keratinocytes, and on the other hand, melanocytes secrete a series of substances which act upon keratinocytes Through extensions, the melanosomes of melanocytes are transferred to the surrounding keratinocytes 17 , where they distribute uniformly in order to insure a homogeneous pigmentation and create a screen which covers the nucleus of keratinocytes The transfer of the mature melanosomes to keratinocytes takes place when the pH of the extracellular environment increases from 5.

Moreover, the number of dendrites of melanocytes, as well as the transfer rate of melanosomes at the level of epidermal unity is influenced by exposure to the sun ultraviolet radiation Due to this placement, melanin protects the nuclear DNA from ultraviolet rays of solar light The pigmentation process has the effect of increasing human skin resistance to sun burns An important role in the differentiation, proliferation and morphology of melanocytes has the glutamate pathway by activating the epidermal glutamate receptors At the level of melanocytes and keratinocytes the glutamate receptors have been described The differences in the human skin pigmentation appear due to the various number of melanosomes in the keratinocytes In order to fulfil the basic function, the life span and melanocyte resistance must be high.

At the level of hair follicle, the melanic pigment synthesis takes place in the follicle unit made up of the follicle melanocytes, keratinocytes and the dermic papillary fibroblasts 22 which, compared to the epidermal unit, is larger. Synthesis of the melanic pigments in the skin is an ongoing process at the level of hair follicle.