Tumour-inducing capacity found in sleeping cancer cells

2018 - 02 - 08

A ground-breaking study involving LIH was published in Nature in December 2017, showing that chemotherapy-induced senescent lymphoma cells have a very high tumour initiation potential when returning from senescence. The findings could have an impact on cancer therapies.

The research work was led by Prof Clemens Schmitt from the Charité-University Medical Centre and the Max-Delbrück-Centre for Molecular Medicine in Berlin, Germany. For this study, he teamed up with Dr Gunnar Dittmar, Head of the Proteome and Genome Research Unit at LIH’s Department of Oncology, to investigate the changes that are undergoing during treatment with chemotherapeutics. Chemotherapy can act in different ways on cancer cells and does not always kill them. It can cause severe DNA damage that puts the cells into a senescent or “sleeping” state in which they do not divide anymore. Cancer cell senescence and its consequences for clinical applications of chemotherapeutics were not understood in detail yet.

The study describes that a reprogramming involving the Wnt signalling pathway takes place during senescence and confers the cells with specific properties of stem cells - functions being collectively termed “stemness”. When the cells manage to exit senescence, stemness allows them to divide efficiently and become aggressive. When the scientists transplanted previously senescent lymphoma cells into mice, much fewer cells were needed to initiate tumour development compared to when cells that have never been senescent were transplanted. 

The researchers concluded that chemotherapy-induced senescence could generate tumour cells that have an enhanced potential to drive tumour growth if they escape the cell cycle arrest. The findings of this study provide new mechanistic insights into the plasticity of cancer cells, but should most importantly have an impact on anti-cancer therapies. The authors state that new pharmacological strategies need to be developed to accurately eliminate senescent cells before a fraction of them make use of their acquired stemness capacity and cause tumour relapse.

Link to publication: Milanovic et al. Senescence-associated reprogramming promotes cancer stemness, Nature (2017).