  Background: A fundamental problem in cancer research is identifying the cell
type that is capable of sustaining neoplastic growth and its origin from normal
tissue cells. Recent investigations of a variety of tumor types have shown that
phenotypically identifiable and isolable subfractions of cells possess the
tumor-forming ability. In the present paper, using two lineage-related human
melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative
line IGR37, two main observations are reported. The first one is the first
phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs)
from mutated tissue-specific stem cells; and the second one is the
identification of a more aggressive subpopulation of CSCs in melanoma that are
CXCR6+. Conclusions/Significance: The association of a more aggressive tumor
phenotype with asymmetric self-renewal phenotype reveals a previously
unrecognized aspect of tumor cell physiology. Namely, the retention of some
tissue-specific stem cell attributes, like the ability to asymmetrically
self-renew, impacts the natural history of human tumor development. Knowledge
of this new aspect of tumor development and progression may provide new targets
for cancer prevention and treatment.
