Induction characterization and targeting of human hematopoietic cancer stem cells.

Abstract

Tumors contain a minority population of cancer stem cells (CSC) that maintain the tumor. In marked contrast to the CSC, the tumor cells have either no capacity or a markedly diminished capacity, to form new tumors. Therefore, to treat cancer effectively, the CSC must be eliminated. The tumor will rapidly recur if the therapy eliminates cancer cells but spares a significant population of the cancer stem cells. We report here for the first time the utilization of the SCID-hu Thy/Liv chimeric small animal model system for induction of human cancer stem cells and their early detection. This model system allows long-term systemic human T-cell reconstitution in vivo, and also provides both human antigen-presenting cells (APCs) and effector cells for induction of anti-tumor immune responses. We were able to generate human hematopoietic cancer stem cells (HCSC) using the SCID-hu Thy/Liv system, and confirmed the expression of both the CD34 marker and two human tumor antigens in these cells. Importantly, we observed an enhanced expression of several embryonic stem cell markers in the HCSC, as well as morphological appearance typical for undifferentiated cells, suggesting the acquisition of highly malignant aggressive properties. Therefore, these findings are an important step in our understanding of the mechanisms involved in the early formation of the cancer stem cells, and in demonstrating the stem cell origin of cancer.