Tumour Stem Cell Enrichment by Anticancer Drugs: A Potential Mechanism of Tumour Recurrence

Abstract

Tumour recurrence after chemotherapy is a serious clinical problem. An emerging concept in tumour biology is the cancer stem cell hypothesis, which emphasises the importance of rare tumour stem cell-like cells to reinitiate the tumour even after a successful elimination of the primary tumour mass by surgery, chemotherapy or radiotherapy. We employed live cell tools to monitor caspase-mediated cell death or survival after in vitro drug treatment to investigate events associated with enrichment of CSCs in breast and colon cancer cells. We provide evidence for rare escape of cells from drug-induced caspase activation that enriches cells with stem cell-like cells. Interestingly, an intermediate senescent-dominating population was evident during the transition and the post-senescent; drug-surviving cells were enriched with dye efflux cells with embryonic stem cell markers. Since senescence-escaped stable colonies generated are enriched with stem cell-like phenotype from natural tumour cell models and also stably express sensitive caspase sensor, in the future they can be utilised for screening compounds that target them.