The survey, conducted by the CSIC, defines a potential strategy for the design of future treatments for disease.
A team at the Consejo Superior de Investigaciones Científicas (CSIC) has discovered the mechanism by which the enzyme MMP-9 affects the survival of cells of B chronic lymphocytic leukemia (CLL-B) and allows the spread of the disease.
The finding, which appears in the February issue of the journal Cancer Cell, explains why they have failed the clinical trials have been conducted targeting this enzyme and defines a potential strategy for the design of future treatments for disease.
As explained by the director of research, Angeles Garcia Pardo, a research professor of the CSIC, B-CLL is characterized by the accumulation of abnormal B lymphocytes in peripheral blood, which circulates throughout the body.
As the disease progresses these cells are distributed throughout the body via the blood and reach lymphoid organs, such as bone marrow and lymph. This prevents the normal functioning of normal B cells, vital components of the defensive line of human beings, and the action of the disease results in death.
Garcia Pardo and his team of the CSIC in Madrid with the collaboration of hematologists University Hospital Puerta de Hierro in Madrid, and the Clinical Hospital of Valencia, as well as with scientists from the University of Louvain (Belgium), Justus Liebig University (Germany).
The group has studied the mechanisms involved in migration and survival of B-CLL cells, ie the processes that lead to disease spread. Have focused on matrix metalloproteinase-9 (MMP-9), an enzyme that degrades the extracellular matrix, the medium in which cells are embedded, which facilitates the progress of B-CLL cells.
Along with this capability, already known to degrade substrates and pave the way for the disease, the CSIC group have discovered a new role for MMP-9: to ensure the survival of B-CLL cells, through binding to specific receptors on its membrane and induction of intracellular signals. This new feature does not require the enzymatic activity of MMP-9, but is located in another region of the molecule, called hemopexin domain.
“The finding is relevant because, so far, clinical trials have been to placate the action of MMP-9 enzyme that degrades substrates and have not had the expected success. Our work provides an explanation for these failures and define the region cell which produces the connection between MMP-9 and malignant cells as a new target for the design of treatments against this leukemia, “he concludes.