Researchers uncover how breast cancer tumor cells break free and form metastases

Breast tumor cell attempting escape. Image: Renaud Poincloux & Philippe Chavrier/CNRS/Institut Curie

Discoveries by researchers at the Institut Curie in Paris may help shed light on why some breast cancers are more aggressive than others.

Attempted cell escape. This scanning electron microscope image shows breast tumor cell (pink) on a thick layer of Matrigel (green), which mimics the basement membrane separating the body’s tissues. This highly invasive cell penetrates the Matrigel layer and “escapes” in a process similar to that of the invasion by tumor cells. 

Two new discoveries by researchers at the Institut Curie in Paris may help shed light on why some breast cancers are more aggressive than others. The discoveries could lead to earlier identification of highly invasive tumors and the ability to block metastases formation, according to the researchers.

When tumor cells acquire the capacity to move around and invade other tissues, there is a risk of metastases and cancer treatment becomes more difficult. A team led by research director Phillippe Chavrier has discovered how breast cancer cells break the bonds that tether them to the tumor. The basement membrane around the mammary gland is a barrier to the spread of cancer cells. Three proteins in the tumor cells transport enzymes needed to perforate this barrier, and another protein puts these enzymes in the right place.

Tissues are generally formed by cells arranged side by side. Epithelial cells cover an outer surface, such as the skin or an organ such as the mammary gland, and remain tightly bound together. This cohesion is vital to the body’s functioning, and the epithelial cells remain in position in their original tissue until they die. Sometimes, though, they detach and move away, and while such migration is essential during embryonic development as cells give rise to new tissues, when tumor cells break loose this often heralds the formation of metastases.

The cell first forms protrusions called invadopodia and anchors them in the basement membrane. These “feet” provide everything needed to breach the membrane. The tumor cells produce a whole range of proteases that degrade the proteins of the extracellular matrix that hems them in, part of which is the basement membrane. These proteases cut a hole in the basement membrane through which the cells can escape.