Departing from the script
Countdown to catastrophe: Tumor biologist Heiko Hermeking studies the factors that cause cells to disregard natural constraints and opt out of their assigned roles in differentiated tissues.
All cancers originate in a loss of control, when a single cell suddenly begins to divide more often than it should. Under the microscope, the deregulated cell cannot be distinguished from its neighbors in the same tissue or organ, and its progeny also look normal.
It takes time for such misfits in a homogeneous cell mass to become recognizable as being different from the cells around them. And by this time, the tumor has taken on a life of its own. Molecular biologist Heiko Hermeking at LMU’s Institute of Pathology, wants to understand why.
Tumor cells in disguise
Hermeking compares the tumor cell with a vehicle in which the accelerator pedal is stuck in position. Whether a car is travelling at 100 km/h on the autobahn or racing at top speed when this happens can make a big difference to the outcome, but slowly growing tumors can actually be more dangerous than the rapidly growing ones, he says. Fast-growing tumors tend to provoke the body’s immune system into mounting a counterattack that eliminates the rogue cells. Slowly growing ones are more likely to evade detection. And tumors that can continue to grow for many years are bad news, he explains. “Genetic changes which do not immediately cause chaos and force cells to commit suicide are often the more dangerous ones,” says Hermeking.
So keeping the accelerator pressed to the floor is usually not a good strategy for a growing tumor – although Hermeking prefers not to use the term “strategy” when it comes to tumors. “A tumor does not behave as it does because it is following a well thought out plan,” he points out. “On the contrary, a tumor results from a local breakdown in the system. Tumor cells are subject to the rules of evolution, he says. They simply make use of the biological possibilities provided by their genetic apparatus, which determines the metabolic capacities they possess and the complement of molecules they produce. And for the past 25 years, Hermeking has been probing how this process of adaptation works.
Hermeking has been based in the Institute of Pathology at LMU for the past 6 years. Visitors who enter the building from the Winckelstrasse embark on a journey through time. Columned halls, broad staircases, busts of former directors arrayed in niches along the walls. The succession stretches back for nearly a century. Max Borst, for instance, was Director when the building was opened in 1928 (its construction took only 2 years) as a replacement for the old Institute on Nussbaumstrasse, which was no longer large enough to serve its original purpose. Borst was responsible for developing a method for the “histogenetic definition of tumors”. This provided a systematic method for the differentiation of tumor types classifying tumors, and still serves as the basis for the classification scheme used by the World Health Organization. The aura of a bygone age persists when one enters the wing in which the laboratories are located – but not for long! It soon becomes clear that time has not come to a standstill here.
Modern laboratory equipment is everywhere. “Pathologists here examine some 50,000 tissue samples every year,” says Hermeking – mostly in order to determine whether a patient’s tumor is benign or malignant. He himself is only indirectly concerned with such histopathological investigations however.
When Ludwig von Buhl took over the direction of Munich University’s first Institute of Pathology on Nussbaumstrasse in 1875, he seems to have divined how the subject would develop. When the Institute opened, he declared that it would “permit a division of labor, focusing not only on pathological anatomy and histology, but also on chemical, physical and experimental studies, with a view to understanding the nature of pathological phenomena and defining the conditions that give rise to them. In other words, from the beginning, observational diagnostics and microscopy have co-existed alongside chemical, physical and biological – in short, experimental – methods, in the quest for a better understanding of cancer and more effective ways of fighting it. The complementarity between basic, experimental research – such as that in which Hermeking is engaged – and clinical diagnostics remains constitutive.
As Head of the Laboratory for Experimental and Molecular Pathology, Hermeking is a dedicated basic researcher, but he collaborates closely with his clinical colleagues. However, his own “patients” are four-legged creatures. Whenever the problem in hand cannot be answered in cell culture systems, his group turns to the mouse as an experimental model organism.