Cancer therapies approach to disabling tumor development discovered

Molecular switch identified for destruction of cancer cells?
In a recent study, scientists from the University of Freiburg in Breisgau have shown how a protein prevents the uncontrolled spread of defense cells. This opens new approaches for the treatment of various cancers, including acute lymphocytic leukemia (B-ALL), the most common type of cancer in children.

In their study, the researchers led by Professor Michael Reth from the Albert-Ludwigs-University Freiburg prove, how a so called B lymphocyte influences a certain protein and thus prevents the development of tumor cells. The researchers published their results in the renowned journal "Nature Immunology".

A kind of molecular switch could stop the formation of tumor cells in acute lymphoblastic leukemia and other cancers. (Image: psdesign1 / fotolia.com)

Immune cells become mature lymphocytes
The human immune system consists of millions of individual cells that are produced in the bone marrow from precursor cells every day, explain the scientists. The immune cells expand in the course of their development and differentiate into mature lymphocytes. These defense cells can recognize and eliminate foreign substances. Such alternating phases between proliferation and differentiation are also found in the maturation of B lymphocytes, which are able to form antibodies, the scientists explain.

Switch with two components
In their recent studies, the researchers have investigated how the "switch" works, which controls the transition between both phases in B lymphocytes. "By controlling the transition between the two phases, the switch limits the expansion phase of the precursor cells, the so-called pre-B cells," the scientists report in a press release from the University of Freiburg. If these pre-B cells multiply indefinitely, this could lead to pre-B cell leukemias. Professor Reth and colleagues were able to prove that the switch consists of a complex with two components - the adapter protein B-cell translocation gene 2 (BTG2) and the protein arginine methyltransferase1 (PRMT1).

Propagation of tumor cells stopped
Normally, BTG2 is upregulated in differentiating progenitor cells, Dr. Elmar Dolezal, first author of the study. If the production of BTG2 was triggered in pre-B cells, their multiplication stopped immediately. The co-author dr. David Medgyesi explains how the BTG2 / PRMT1 complex stops the expansion of pre-B cells: "After binding BTG2, PRMT1 methylates the CDK4 protein, thereby preventing its function in the cell cycle and further cell proliferation," he says expert.

BTG2 gene turned off in many tumor cell
Interestingly, according to the researchers, many tumor cells have lost or immobilized the BTG2 gene. For example, this is hardly found in the tumors of B-cell acute lymphoblastic leukemia (B-ALL), which is the most common type of tumor in children. In the mouse model, the scientists were able to show that the reintroduction of BTG2 into such B-ALL tumor cells prevents further tumor development, which brings hope for new treatment options.

Hope for new treatment options
The researchers said they "discovered how BTG2 acts as a tumor suppressor in pre-B cells," leading to a "better understanding and possibly better treatment of B-ALL tumor disease." In the future, it will be important to "understand the exact mechanisms of expression and regulation of the BTG2 gene and find ways to introduce BTG2 into B-cell tumors in patients, thus blocking the expansion of tumor cells," says Professor Michael Reth. (Fp)