Alberto J. Schuhmacher
ARAID researcher and head of the Molecular Oncology Group at the Aragón Health Research Institute (IIS Aragón)
Cancer is an organised cellular crime, it is not just about cells with mutations that grow out of control. Tumour cells establish a molecular dialogue with their environment and modify it to grow and become malignant. In order to spread and form metastases, tumour cells must leave through the bloodstream, nest and grow in other organs that are different from the one of origin and, therefore, the new environment that surrounds them is different. Sometimes, the tumour sends molecules that modify the target organ, forming a ‘pre-metastatic niche’ so that the tumour cells that have migrated can establish themselves more easily.
Obesity is associated with a higher risk of developing breast cancer and more metastasis. This research shows us some of the mechanisms that explain how obesity derived from a high-fat diet can facilitate metastasis. It is well known that obesity promotes blood clotting. In this work, Héctor Peinado's team elegantly and with much evidence shows how, in obese mice fed a very fatty diet, platelet aggregates form that can surround cells escaping from the tumour and act as an ‘invisibility suit’ so that the defences do not recognise them.
In addition, they found that with this diet special ‘pre-metastatic niches’ are formed in the lung, these ‘adipo-niches’ are enriched with a protein called fibronectin. The union of activated platelets and these ‘adipo-niches’ favours the formation of more metastases and better growth in mouse models of triple negative breast cancer.
Blood samples from 82 women with triple-negative breast cancer obtained before they were operated on and treated with chemotherapy were then analysed and it was found that coagulation was increased in obese patients, but they did not observe a higher risk of relapse and metastasis at five years associated with body mass index. We must remember that these people are receiving treatment; experimental models allow us to explore questions that sometimes cannot be asked in the clinic. Thus, this research opens the door to identifying additional risk factors and allows us to analyse forms of dietary intervention or platelet activity control, which help to improve the way we treat these patients and improve their lives.