I spent last five years studying inherited colorectal cancer (CRC), known as Lynch syndrome, which is common in people who get a mutation in one of mismatch repair genes from their parents. Later I got interested in sporadic CRC and how environment influence cancer development.
Fig. 1 Schematic colon crypt. Differentiated cells in blue, transient amplifying cells in red, green cells are stem cells, and yellow are goblet/endocrine cells.
Colorectal cancer develops as a result of multi-step tumorigenesis. It is known that 5-7 mutations in tumor suppressor genes and oncogenes are needed for high grade carcinoma. Genetic mutations are definite drivers of tumorigenesis but not the only one. Western Style diet (WD) has been associated with increased CRC. My previous and ongoing studies on WD induced proteomic changes in normal colon mucosa have shown that metabolism of fatty acids and bile acids have larger effect on proliferative mechanisms than previously anticipated (Dermadi Bebek, Valo et al. 2014).
Recent results suggest complex interaction between different protein networks, which sometimes on the first sight look controversial. My gut feeling is suggesting that none of them are controversial, and all are equally true.
Let me take a step back and introduce structure of the colon crypt. As I work with mouse, I’ll use mouse colon as a model. Colon consists of crypts, which have hierarchically well defined structure (Fig.1). As you can see even in this overly simplified figure not all cells are the same, even less, equal. But there are many more cells that crawl in our colon - between the crypts (dark pink areas (Fig. 1): different types of immune cells and outside the crypts, from the side of the lumen, numerous microorganisms.
In a healthy individual all those cells live in a finely tuned balance, which is regulated heavily by signals, mainly consisted of small molecules, hormones and proteins. Principle of action and reaction known in physics, exists in biology, too. Maybe cells do not push each other, but they do poke with molecules. Some signals come from the surrounding cells, others from the environment, such as molecules derived from food we digest. Food itself is not toxic, but it has tremendous effect on massive number of biochemical reactions that are happening every second in our cells. With that in mind, if we flush our cells for years with molecules derived from food that is not healthy like Western diet, we are actually pushing our cells out of balance, little by little. It is only normal that they will react on conditioning caused by environment in order to achieve new balance.
“Western style diet is scarce on fiber, calcium, vitamin D, folate, but rich on simple sugars and fats of animal origin.”
The question is: what will new balance do to our cells? Western diet is associated with increased CRC, but mechanisms are largely unknown. Can it be that WD with unhealthy fats, simple sugars, low vitamins and fiber modulates cell environment, which favours cancerous cells? It is reasonable to think that Western diet could naturally select normal cells, which are prone to slip over the brink into the abyss of tumorigenesis.
How to study these complex mechanisms and signals? We tried to tackle and dissect main changes in normal colon tissue, but many appeared controversial, and pointed to reactions that are cancelling each other. In other words, detected mechanisms behaved very much like action reaction principle. I would dare to say we detected cellular chat, but unfortunately at present resolution we weren't able to point which cell types talked what to each other.
In order to enhance resolution and define types of cells, which are sending important messages similar study with single cell approach should be performed. Most certainly we would be able to see trees from the forest.
For more insights and news how our diet interacts with our genetcis stay tuned.