Exploring metastatic dormancy to tackle breast cancer metastasis


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Stefania Di Blasio1,Laurie J Gay1,Ilaria Malanchi1
1The Francis Crick Institute

Abstract

Background

Over ninety percent of breast cancer-related death are caused by metastasis. Disseminated tumour cells (DTCs), that have reached distant organs via circulation, can remain within the host tissue without outgrowing. This phenomenon is known as metastatic dormancy. Albeit non proliferative, DTCs retain their capacity to originate metastasis several years after cancer is first diagnosed. The cause of their reactivation is largely unknown. Recent studies have suggested that an unhealthy lifestyle, such as tobacco smoking or high-fat diet, has a dramatic effect on the homeostasis of healthy tissues. Indeed, high-fat diet was shown to induce important systemic perturbations in the inflammatory compartment. These effect, associated to poor lifestyle factors, may induce dormant DTCs to awaken and outgrow. Here, we focus on the potential effects of obesity and inflammation to perturb the bone microenvironment, causing metastatic reactivation.

Method

We employ a novel experimental approach where metastatic competent cells are pushed into dormancy by an in vivo engineered dormant-permissible tissue. Of note, our strategy does not require the use of cancer cells intrinsically unable to grow in vivo, thereby recapitulating clinical features of breast cancer metastasis to the bone.

Results

We aim at dissecting the interaction between cancer cells and the components responsible for the switch of a dormant niche supporting quiescence, to a pro-metastatic niche supporting cancer growth.

Conclusion

The outcome of this study will provide insights into molecular drug targets on DTCs, that can be combined with factors specifically triggering pro-metastatic niche components activity, for tackling breast cancer metastasis.