An experimental therapy can promote metastasis of triple-negative breast cancer. This is shown by cell biologist dr. Erik Danen and his team at the University of Leiden, The Netherlands. If you disable integrins, cell surface molecules important for adhesion, cancer cell do not die but become more motile. “An unexpected result”, according to Danen.
The experimental therapy is being investigated in several places around the world and is in early stages of clinical trials. The approach works by inhibiting cell adhesion receptors on the cancer cells, the integrins. As a result the cell don’t receive growth signals anymore, making it harder for them to survive and makes them more sensitive for classical therapies, like chemotherapy or radiation therapy. The research by Danen and colleagues shows an additional effect. “Inhibiting the ‘little feet’ from the cells results in the cells becoming more motile. In case of triple-negative breast cancer, the tumor shrunk, but more metastasis arose”, says Danen.
Danen and his colleagues cultured β1-integrin deficient triple-negative breast cancer cells and injected them in mice. Danen: “Additional research showed that removing the integrins leads to the activation of an embryonic program in these cells. This program is essential in embryos, but dangerous in cancer cells.” Activation of this signaling network enables the cells to move individually, instead of as groups, thereby promoting metastasis.
The team from Leiden uncovered that signaling pathway through TGFβ is involved in the activation of this program. “Since we now know the signaling pathway involved, we can develop a new therapy that inactivates the integrins, but combines this with an addition inhibitor to prevent the initiation of the embryonic program”, Danen explains.
Thus far, this was only studies in triple-negative breast cancer cells. Additional research is needed to show if the activation of the embryonic program also occurs in other types of cancer cells. Danen: “We already saw that one specific type of triple-negative breast cancer cell does stop moving if we disable integrins. Apparently, these cells are not able to activate the program and move as single cells. Now we want to find out for which other forms of cancer this applies.” Danen suggests that at least with triple-negative breast cancer caution is needed with this type of therapies.
Danen: “This research has consequences for the development of this kind of new cancer therapies. It shows that we have to be careful with inhibiting integrins. Negative side effects that we had not predicted on forehand can occur.”
The research is published in Science Signaling on February 11th.