An all-Italian study shows that interleukin-4 produced by tumor cells and cells in the surrounding microenvironment favors the progression of breast cancer, paving the way for new therapeutic developments.
In oncological research it can happen that some results, in addition to being relevant in themselves, open the way to new lines of investigation that help to clarify the biology of the tumor. The group of Prof Matilde Todaro of the University of Palermo, has observed that several tumors are characterized by high concentrations of a molecule of the immune system called interleukin-4 (IL-4). The observation is the basis of a recent study that showed how, in breast cancer, IL-4 is essential for the development of metastases and resistance to anti-cancer therapies.
First, the researchers found higher concentrations of IL-4 in triple negative breast tumors, which are more aggressive and tend to give metastases. A long series of experiments in isolated cells and with laboratory animals has allowed to define the molecular mechanisms that lead this molecule to promote tumor progression. “IL-4 – explains Todaro – works by activating the transcription factor NF-kB, which in turn inhibits the DUSP-4 molecule”. In practice all this translates into a “push” favorable to the tumor. To confirm their hypothesis, the researchers conducted other experiments with laboratory animals, demonstrating that if the concentration of DUSP-4 is lowered it is possible to transform non-metastatic tumors into metastatic tumors and vice versa.
These results, obtained thanks to the fundamental support of AIRC and published in the journal Cancer Research, are significant for two reasons. Firstly, they underline once again the importance of the microenvironment for the progression of the tumor. “The IL-4 is in fact produced both by the tumor cells and by the cells present in the tumor microenvironment, for example by the cells of the adipose tissue. This discovery, therefore, reinforces the link already known between obesity and breast cancer, “explains Todaro. Secondly, it opens up a new therapeutic perspective. “There are already NF-kB inhibitors that could be tested in breast tumors that have elevated IL-4 concentrations: this could be the case if the risk of metastasis is reduced”.