Preventing metastasis by stopping cancer cells from making fat
University of Louvain researchers have shown that lipid storage in cancer cells promotes metastasis. A new drug currently being tested to treat obesity may also help fight metastasis. Credit: University of Louvain
Researchers led by Prof. Olivier Feron, at the University of Louvain (UCLouvain) Institute of Experimental and Clinical Research, seek to understand how tumor metastases form. In prior studies, they have demonstrated that the most aggressive cancer cells use significant amounts of lipids as energy sources. In the latest research, Prof. Feron and his team have discovered that cancer cells store lipids in small intracellular vesicles called ‘lipid droplets’. Cancer cells loaded with lipids are more invasive and therefore more likely to form metastases. The research team sought to identify the link between lipid storage and metastasis.
They identified transforming growth factor-beta 2 (TGF-beta2) as the switch responsible for both lipid storage and the aggressive nature of cancer cells. Moreover, it appeared that the two processes were mutually reinforcing. In fact, by accumulating lipids, more precisely fatty acids, cancer cells build up energy reserves, which they use as needed throughout their metastatic course.
The acidity found in tumors has been shown to promote cancer cell invasion of healthy tissues. The process requires the detachment of the cancer cell from its original anchor site and the ability to survive under such conditions, which are fatal to normal cells.
UCLouvain researchers demonstrated that this acidity promotes, via the same TGF-beta2 ‘switch’, the invasive potential and formation of lipid droplets. These provide the invasive cells with the energy they need to move around and withstand the harsh conditions encountered during the metastasis process. It’s like a mountaineer who takes the food and equipment necessary to reach the summit in spite of complex weather conditions.
The research findings open up new therapeutic avenues thanks to the discovery of the different actors involved in metastasis. These actors can thus be targeted and combated. Prof. Feron and his team have shown that it is possible to reduce tumor invasiveness and prevent metastases using specific inhibitors of TGF-beta2 expression but also compounds capable of blocking the transport of fatty acids or the formation of triglycerides. Among the latter are new drugs that are being evaluated to treat obesity. Their findings could potentially be rapidly applied to counter the development of metastases, which is the major cause of death among cancer patients.
The study is published in the prestigious scientific journal Nature Communications. The research was carried out with funding from the Belgian Cancer Foundation, the Belgian National Fund for Scientific Research, the Télévie telethon, and a Wallonia Brussels Federation joint research grant (ARC).
Materials provided by the Université Catholique de Louvain. Content may be edited for clarity, style, and length.