Identification of cancer stem cells in human melanomas

Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. According to the cancer stem cell hypothesis, only a subpopulation of cells within a cancer has the capacity to sustain tumor growth. This subpopulation of cells is made up of cancer stem cells, which are defined as the population of cells within a tumor that can self-renew, differentiate, and generate a phenocopy of the cancer when injected in vivo. Cancer stem cells have been prospectively isolated from human cancers of the blood, breast, and brain. Several evidences strongly suggest that melanocytic neoplasias are derived from immature melanocytic cells, which are neural crest derived, and we thus hypothesize that melanoma develops from mutated neural crest stem cells. Accordingly, at least a fraction of melanoma cells should display features of neural crest stem cells. I have evidence that metastatic human melanomas, as well as established human melanoma cell lines, contain a cell subpopulation resembling neural crest stem cells. These cells are potent in tumor formation when a limited number of cells are injected into an orthotopic in vivo microenvironment. Very importantly, this cell population is able to self-renew and can generate melanoma after serial transplantation when re-isolated from secondary recipients. Moreover, these tumors contain the cell types observed in the original cancer. These results all together strongly support that melanomas are generated by cancer stem cells with characteristics similar to neural crest stem cells. The identification of cancer stem cells in melanoma has fundamental implications for the development of new therapeutic agents. Eradication of cancer may require the targeting and elimination of cancer stem cells.

© 2010 Gianluca Civenni