Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females in the western world1 . Increasing evidence suggests that tumor recurrences and metastatic processes are due to a subpopulation of tumor cells known as tumor-initiating cells (TICs)2-3 , which are endowed with properties of chemo- and radio- resistance, self-renewal and multi-lineage differentiation capacity4-6 . Several different potential colorectal TIC markers have been identified as gauged by tumor seeding ability, sphere formation and cell surface marker expression including CD247 , CD268 , CD449 , CD13310-11 and ALDH1A112 .
Using a novel in vitro culture method we utilize the chemoresistance property of TICs to examine both acute and prolonged effects of chemotherapy treatment on the aforementioned TIC subpopulations. We identify two morphologically and phenotypically distinct subpopulations which emerge after treatment of human colorectal cancer cells, and demonstrate the presence of these populations in patient tumor samples. These findings may be used to establish better therapeutic monitoring paradigms for markers of poor chemotherapy responsiveness, as well as specific targets for development of new therapeutic strategies.