Cell Plasticity and Cancer, INSERM U908, Université de Lille
“Reborn from fire, or how non-cancer stem cells reprogram as CSC under radiation-induced inflammatory chemokines stimulation”
the work summed up:
Cancer stem cell (CSC) identification in solid and hematologic tumors has paved the way to many fundamental and translational studies. However, recent studies have depicted the presence of cancer stem cell plasticity. Indeed, differentiated breast cancer cells (non-CSCs) can generate iCSCs (induced CSCs) in response to various stimuli. Nevertheless, reprogramming mechanisms remain unknown, and strategies to reduce the reprogramming of non-CSCs into iCSCs might prevent treatment-resilient cancer cells driving recurrences. We demonstrated, for the first time, that chemokines are involved in reprogramming and can be used to target radiation-induced CSC enrichment. In combination with radiation treatment, inhibition of these chemokines allows increased survival of mice in xenograft model. We also demonstrated that the expression of chemokines and their receptors is associated with CSC profiles in tumor patients. More interestingly, expression of specific chemokines or their receptors could be useful as prediction markers. We are actually investigating intracellular mechanisms driving anti-cancer treatments-induced reprogramming. Also, we are developing the first animal transgenic model to track and distinguish CSCs from iCSCs, and so to study in vivo reprogramming.