Stem-cell hierarchy in skin cancer

Cancer is not a cell-autonomous disease, but involves disruption of the complex system of controls exerted by the local microenvironment, as well as hormonal or immune-system components produced by the whole organism.Cancer, like any other tissue that is capable of regeneration or progressive growth, must have cells with self-renewal capacity and a hierarchical architecture.Although many tumours contain cells with the characteristics of stem cells, the identity of the normal cells that acquire the first genetic hits leading to initiation of carcinogenesis has remained elusive. Although expression of stem-cell markers might reflect the tumour cell of origin, it remains possible that these markers are induced by the oncogenic events that occur after the initiation of neoplastic growth.It is likely that there is a continuum of target cells for carcinogenesis, and that combinations of the particular cells in which mutations occur, as well as the specific genes altered, are the main determinants of cell fate and malignant potential.Tumour promoters, which are not in themselves mutagenic, might affect the specific choice of initiated cell that forms a visible lesion and allows the selection of particular target cells.Oncogenic events allow proliferation and self-renewal genetic programmes to be reconciled within the developing tumour.