How breast cancer cells metastasize

Scientists at the Curie Institute, working under the leadership of Dr. Philippe Chavrier, have deciphered the mechanism by which breast cancer cells break away from the tumor and form metastases.

Usually, tissues consist of cells tightly adjacent to each other. Under certain conditions, cells acquire the ability to break away from the tissue and move around the body. Cell migration is very important during embryonic development, while in an adult organism, tumor cells that move around the body and form metastases in organs remote from the tumor usually acquire this ability.

As the tumor develops, its constituent cells accumulate genetic errors, which further aggravates their abnormality. Some of them acquire the ability to separate from the tumor with the help of complex and poorly understood mechanisms. The authors managed to partially decipher these mechanisms used by breast cancer cells. The peculiarity in this case is that the basement membrane surrounding the mammary gland is a barrier to the spread of malignant cells throughout the body.

To overcome this barrier, tumor cells form protrusions – invadopodia – and fix them on the basement membrane. After that, they begin to synthesize a complex of enzymes-proteases that destroy proteins of the intercellular substance, including the basement membrane. As a result, a "hole" is formed in the membrane through which the cell leaves the mammary gland.

First, using a model of metastatic breast cancer cells, the authors demonstrated that sec3, sec8 and IQGAP1 proteins transport protease-filled vesicles (membrane vesicles) from the site of enzyme synthesis in the invadopodia.

Further, they found that the Vamp7 protein ensures the fusion of protease-containing vesicles with the tumor cell membrane. After that, the proteases that appeared at the ends of the invadopodia gradually corrode the basement membrane of the mammary gland. Inactivation of the Vamp7 protein significantly reduces the ability of breast cancer cells to destroy the intercellular substance.

Thus, in order to leave the mammary gland, tumor cells must undergo a whole complex of modifications. The authors demonstrated that due to the changes occurring with them, such cells acquire the ability to use cellular mechanisms for their spread and the formation of metastases.

The findings made by the authors will help not only to explain why some tumors are more aggressive than others, but also to develop methods to identify highly invasive tumors at early stages and, possibly, even prevent metastasis.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily

14.07.2008