The Role of Lipids in Metastasis Offers Therapeutic Targets that May Work for Many Cancers

The primary mechanism by which most cancers kill patients is metastasis, the spread of cancerous cells from the original tumor to new locations throughout the body. If metastasis didn't exist, cancer would be a much more tractable problem, largely capable of being controlled via even the blunt approach of surgery. Research that might lead to ways to sabotage metastasis across many different types of cancer is thus of great interest. A number of possible approaches have emerged over the past decade or so, but none have as yet advanced to the point of practical application in the clinic.

Researchers have demonstrated that the most aggressive cancer cells use significant amounts of lipids as energy sources, and 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. Researchers identified a factor called 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 can then use as needed throughout their metastatic course.

Already known was that the acidity found in tumours promotes cancer cells' invasion of healthy tissue. 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 healthy cells). The new finding: 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 process of metastatis.

Concretely, this research opens up new therapeutic avenues thanks to the discovery of the different actors involved in metastasis, as these actors can be targeted and combated. Researchers show that it is possible to reduce tumour 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 indications could therefore be rapidly extended to counter the development of metastases, which is the major cause of death among cancer patients.


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