Ung thư tế bào gốc lý thuyết và thực hành Để ủng hộ sự xuất hiện của CSCS một số thay đổi sẽ xảy ra như: thay đổi trong các vi môi trường thích hợp, biểu sinh Phi điều tiết và các đột biến trong gen cụ thể chịu trách nhiệm về sự thay đổi trong chu kỳ tế bào, mô hình khác biệt, tự đổi mới và các quá trình trao đổi chất và cuối cùng, khuếch đại của bị biến đổi di truyền các quần thể này (Bapat, 2007) | 382 Cancer Stem Cells Theories and Practice In order to favor the appearance of CSCs several changes should occur such as changes in the niche microenvironment epigenetic deregulation and mutations in specific genes responsible for alterations in the cell cycle pattern self-renewal metabolism and differentiation processes and finally amplification of these genetically altered populations Bapat 2007 . Differentiated cells Progenitor cell layer Stem cell layer Stroma Normal tissue Pre-cancer tissue T umor Fig. 1. Origin of CSCs. CSCs may arise from the normal SC population due to spontaneous genetic or epigenetic changes or changes induced by disruption of the SC niche stroma X . The acquisition of malignant traits by SCs will be inherited by their progeny grey cells . On the other hand CSC origins could start in a more committed cell progeny through acquisition of selfrenewal properties once again mediated by mutational events and giving rise to modified daughter cells grey cells . Additional modifications of this partially modified progeny and subsequent cell divisions would then lead to the formation of CSCs and a heterogeneous tumor bulk. 3. Cancer stem cell pathways and new opportunities for therapeutic interventions By definition CSCs would maintain the self-renewal and differentiation capacities of SCs thus it is likely that similarities exist in the pathways governing these processes in both normal and CSCs. Understanding the subjacent responsible molecular pathways that regulate these events in normal SCs is therefore extremely important for the design of drugs aimed to destroy CSCs and even avoid tumor relapse. It has been suggested that specific signaling pathways such as Notch Sonic Hedgehog Shh and Wingless Wnt -P-catenin are critical for self-renewal and differentiation in normal stem cells. In agreement with the CSC hypothesis alterations in those genes that encode for signaling molecules belonging to these pathways have been found in human tumor .
