Tuesday, 14 May 2019 10:55

Max Debrück Center Berlin: LTA allows cancer cells to proliferate uncontrollably Featured

Researchers from the Max Delbrück Center for Molecular Medicine in Berlin have discovered an important messenger substance in cell cultures which plays an important role during uncontrolled growth of Hodgkin's lymphoma, a form of lymph gland cancer.

Although Hodgkin's lymphoma is relatively well treatable today, the molecular mechanisms of this cancer are not well understood. In addition, the current therapeutic options are very onerous so that new treatment options are being sought.

A team led by Professor Claus Scheidereit from MDC in cooperation with researchers under the leadership of Professor Stephan Mathas from the MDC and from the University Hospital Charité in Berlin as well as further MDC cooperation partners have taken a closer look at the transcription factor NF-kappa-B with a view to studying why it remains permanent in Hodgkin's cells, in contrast to healthy cells, where it is only sporadic. The scientists used a cell line from the German Collection of Microorganism and Cell Cultures (DSMZ) to investigate which molecules are secreted by Hodgkin's cells that activate NK-kappa-B.

They found out that a messenger substance called LTA (lymphotoxin-alpha) is responsible for this. LTA is secreted by the Hodgkin cells where it activates NF-kappa-B. LTA also drives the production of other messenger substances that contribute to lymphocytes migrating into the lymph nodes where they create a favourable microenvironment for the cancer cells. LTA also ensures that the cancer cells express so-called immune checkpoint ligands that protect them from attacks by the immune system.

In experiments, the scientists succeeded in inhibiting LTA and thereby interrupting NF-kappa-B activity in Hodgkin cells. This could be an approach for new therapeutic treatments.

The scientists have published their findings in the journal Blood:

Linda von Hoff et al (2019). Autocrine LTA signaling drives NF-κB and JAK-STAT activity and myeloid gene expression in Hodgkin lymphoma. Blood. DOI: 10.1182/blood-2018-08-871293.