Biological and Clinical Implications of the Stem Cell Concept in Human Malignancy

Abstract

Further advances in cancer biology and therapeutics depend, among other things, on the development of knowledge of the organization and biological potential of cells within tumors. Two widely supported but extreme views of tumor cell organization have been expressed: 1) the view of tumors as consisting of undifferentiated cells, each with potential for tumor development but with phenotypic heterogeneity imposed by genetic and epigenetic events. Also, often superimposed on this model is the notion of “de-differentiation” which implies that carcinogenesis can occur in differentiated cells which can subsequently re-express the phenotype of more primitive cells. 2) The view of tumors as representing a form of the normal differentiating tissue from which the tumor derived. This implies heterogeneity of cells within tumors with respect to differentiation, and also implies that the likely target for carcinogenesis is the stem cell population. Much of the support for the former view is based on study of transplantable tumors in animals while the importance of cell differentiation has been reinforced mostly by study of spontaneous animal or human tumors.