Metastasis, the strategy adopted by tumor cells to transform into an aggressive form of cancer, are often associated with a gloomy prognosis. Managing to block the metastasis or, even better, prevent their formation would be a giant step towards the fight against cancer. Researchers at Université catholique de Louvain (Belgium) successfully performed this world first on models of human tumors in mice. The results of their study are published online on 24 July in the prestigious journal Cell Reports.
The work by Professor Pierre Sonveaux's team, at Université catholique de Louvain's Institute of Experimental and Clinical Research (IREC), succeeded in pinpointing a family of pharmaceutical compounds whose action prevents the appearance of tumor metastasis. The researchers achieved this tour de force by studying the mitochondria in tumor cells. These organelles are considered as the cells' power station. But when their functioning is altered, as the UCL researchers observed in tumor cells, the mitochondria can promote cell migration, thus leading to the formation of metastasis.
Paolo E. Porporato, a post-doctoral researcher, and other young researchers in Professor Pierre Sonveaux's team, examined the molecular mechanism responsible for the mitochondria's ability to promote metastasis. They succeeded in showing that, under certain conditions, the mitochondria produce more free radicals known as superoxide ions (O2.-). It is this overproduction of superoxide that leads to the formation of metastasis and, consequently, the growth of a tumor.
Involved in other human pathologies such as Parkinson's and Alzheimer's disease, the production of superoxide by the mitochondria can be blocked by very specific antioxidants such as MitoTEMPO. Used in models of murine and human tumors, these compounds turned out to be very efficient at blocking the migration of tumour cells and preventing the spontaneous formation of human tumor metastasis in mice! The discovery of a treatment capable of blocking the mechanism responsible for the formation of metastasis and the existence of a family of promising compounds, is encouragement for their future assessment in a clinical study that aims to validate a preventive treatment against tumor metastasis.
This research was conducted within the framework of projects mainly financed by an ERC Starting Grant, which Pierre Sonveaux obtained in 2009, and support from the F.R.S.-FNRS, Télévie and the Fondation contre le Cancer.
Porporato PE, Payen VL, Pérez-Escuredo J, De Saedeleer CJ, Danhier P, Copetti T, Dhup S, Tardy M, Vazeille T, Bouzin C, Feron O, Michiels C, Gallez B, Sonveaux P. A mitochondrial switch promotes tumor metastasis. Cell Reports (2014), http://dx.
The article will be available for free as of 17:00 on 24 July on the Cell Reports website: http://www.