Tissue Structure Modulates Cancer Development
One of the unusual features of most cancers is that it can take years, even decades, for a pre-cancerous cell to accumulate the many mutations that are needed for that cell to develop into a tumor. In fact, many pre-cancerous cells, and even some microscopic tumors, will have no negative impact on the body at all
Now, using mathematical modeling of evolutionary dynamics, a research group headed by Erik Martens and Oskar Hallatschek of the Max Planck Institute for Dynamics and Self-Organization in GÃ¶ttingen, Germany, may have identified one explanation for this long-observed mystery. In a paper published in the New Journal of Physics, the investigators have shown that the destiny of oncogenic or cancer-causing mutations depends in part on where in the body they occur and how much competition they are exposed to from other, similar mutations in neighboring cells within the same organ.
The modeling experiments showed that in an environment without any spatial structure such as blood, for example, genetic mutations can propagate and accumulate relatively quickly. In tissue with clear spatial structure, such as that of the colon, it takes longer for cells to accumulate the number of mutations required for tumor formation.
The model used in this research was based on the cells that line the intestines. These epithelial cells form many pockets or crypts, each containing isolated groups of cells that may accumulate and carry different mutations. If mutations arise only rarely, they may spread unhindered through the pre-cancerous tissue. However, if other mutations occur before the first one has spread throughout the tissue, the diverse mutation clones meet and compete with one another for survival. In such cases, there are many losers and few winners, and only certain mutations are successful in establishing themselves.
In principle, advantageous mutations cannot proliferate as quickly in spatially structured cell populations as in fully mixed or structureless populations. Consequently, the competition between mutations in spatially structured tissue is often very strong, and the mutation accumulation rate is lower than in non-structured populations. According to the study, this is why structured populations take longer to reach a critical number of mutations, thereby delaying the onset of cancer. The researchers note that their findings could help improve the interpretation of tissue biopsies and contribute to more realistic predictions of cancer progression.
This work is detailed in a paper titled, “Spatial structure increases the waiting time for cancer.” An abstract of this paper is available at the journal’s Website.