To travel into new tissue and create metastases there, cancer cells require a peculiar process. Probably, the same approach maintains some immune cells on their toes. This is the conclusion of a recent study conducted by Bonn University. According to the study, the number of particular structures, the centrioles, increases. This makes it easier for them to maintain their course and travel to lymph nodes, where they activate additional immune cells more rapidly. The findings were just published in the Journal of Cell Biology.
The immune system, like the police, relies on the division of labor. Dendritic cells are the first type of immune cell. They conduct a round-the-clock search for antigens, which are suspicious intruders, in the tissue. If successful, they rush to the lymphatic veins and, from there, to the lymph nodes that drain the lymph fluid. There, they offer their findings to the T cells, a formidable search team. These indigenous forces are now aware of their adversary.
This attack must occur before the intruders inflict significant harm or multiply excessively. Therefore, it is crucial that dendritic cells move as fast as possible to the lymph node briefing. Prof. Dr. Eva Kiermaier of the LIMES Institute (Life and Medical Sciences) at the University of Bonn explains, “We have uncovered a mechanism that assists in this process.” To do so, they produce additional structures known as centrosomes. These allow them to keep their orientation for a longer period of time, allowing them to reach the lymphatic vessels faster. ”
An important function in cell division
Centrosomes are organelles, which are molecular complexes responsible for certain cellular tasks, similar to the organs of the body. Normally, every human cell contains a single centrosome. It doubles just before cell division. The two copies travel to opposite cellular poles and stretch a bundle of fibers, the microtubules, between them. Using them, they separate the duplicated chromosomes during cell division. So, each daughter cell gets a full set of DNA and one of the two centrosomes.
“However, centrosomes are also crucial for arranging the cytoskeleton during cell migration,” says Kiermaier, who was brought to the Rhine from Lower Austria (IST Austria, Klosterneuburg) in 2017 as part of the North Rhine-Westphalia returnee program. This refers to fiber-like structural proteins that provide the cell with form and stability. Additionally, the cytoskeleton determines the “front” and “back” of a cell. This, in turn, changes the direction of its movement.Ann-Kathrin Weier explains, “We have now demonstrated that dendritic cells produce numerous centrosomes upon interaction with an antigen.” The doctoral student at the LIMES Institute and her colleague, Mirka Homrich, are co-first authors of the paper. Both contributed significantly to the experiments.
Staying on course longer in order to achieve the destination faster
Dendritic cells have a dilemma: they do not know the location of the next lymphatic conduit that will lead them to the lymph node. In their search, they employ a “trial and error” methodology: they run in one direction for a short time and then shift course if they have not found a vessel. Mirka Homrich states, “The greater the number of centrosomes an organism has, the longer it stays on course before beginning to look in a new direction.” We were able to demonstrate through computer simulations that this expedites the process of locating lymphatic veins. In the process, the expansion of centrosomes regulates their staying power so that they do not adhere to their direction too tenaciously. This would enhance their likelihood of becoming utterly lost and disoriented.
In healthy cells, the mechanism described in the study was previously unknown. It was hypothesized that cancer cells utilized it to create metastases. However, the increased centrosomes cannot be distributed randomly within the cell. Otherwise, they would substantially interfere with operations like cell division. Therefore, in both tumor cells and dendritic cells, the organelles collect at a single location; they cluster. Kiermaier, who is also a member of the ImmunoSensation2 Cluster of Excellence and the Transdisciplinary Research Area “Life and Health” at the University of Bonn, states, “There are now drugs that disturb this centrosome clustering.” As a result, cancer cells are unable to divide properly and perish.
Nonetheless, it is also possible that these compounds interfere with the immune system, as centrosomes also congregate there. She states that several of these agents have been studied in cell cultures. “We have uncovered evidence that they could considerably weaken the immune system’s effectiveness.” If this were validated in clinical studies, it would be terrible news, as there could be significant adverse effects associated with the use of the active chemicals in cancer therapy.
In addition to the University of Bonn, the Charles University in Vestec, Czech Republic, and the Institutes of Science and Technology in Austria and Spain also took part.
