INTRODUCTION: The lineages assumed by stem cells during hematopoiesis can be identified by the pattern of protein markers present on the surface of cells at different stages of differentiation. Specific antibodies directed at these markers have facilitated the isolation of hematopoietic stem cells by flow cytometry. DISCUSSION: Similarly, stem cells in solid organs also can be identified using cell surface markers. In addition, solid tumors have recently been found to contain small proportions of cells that are capable of proliferation, self-renewal, and differentiation into the various cell types seen in the bulk tumor. Of particular concern, these tumor-initiating cells (termed cancer stem cells when multipotency and self-renewal have been demonstrated) often display characteristics of treatment resistance, particularly to ionizing radiation. Thus, it is important to be able to identify these cells in order to better understand the mechanisms of resistance, and to be able to predict outcome and response to treatment. This depends, of course, on identifying markers that can be used to identify the cells, and for some solid tumors, a specific pattern of cell surface markers is emerging. In breast cancer, for example, the tumor-initiating cells have a characteristic Lin(-)CD44(+)CD24(-/lo) ESA(+) antigenic pattern. In cells derived from some high-grade gliomas, expression of CD133 on the cell surface appears to select for a population of tumor-initiating, treatment resistant cells. CONCLUSION: Because multiple markers, typically examined on single cells using flow cytometry, are used routinely to identify the subpopulation of tumor-initiating cells, and because the number of these cells is small, the challenge remains to detect them in clinical samples and to determine their ability to predict outcome and/or response to treatment, the hallmarks of established biomarkers.
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