The progression of cancer from the very first affected cell to other cells has been observed for the first time by scientists from Boston Children’s Hospital. The study involves the identification of certain genes that might be targeted to prevent cancer from even starting. The findings are published in the journal Science.
Cancer development is marked by mutations that lead to uncontrolled division of cells. Why, then, do some cells exhibit mutations characteristic of the disease without actually behaving like cancerous cells? Could the difference help explain how does cancer start?
The new study focusing on melanoma development in live zebrafish shows that cancer actually starts after an oncogene is activated or a tumour suppressor is lost. Cancer entails a modification that causes a single cell to revert to the stem cell state.
A group of genes are behind the change that pulls a cell back to the stem cell condition, says first author, Charles Kaufman from the Boston Children’s Hospital. Kaufman and his team believe these genes might be made the target of preventive measures for cancer so that the disease does not even start.
The fish that were used for the study all had the human cancer mutation BRAFV600E. They had also lost the tumour suppressor gene p53. Furthermore, they were engineered so that their individual cells would fluoresce green when gene crestin was turned on — this indicates that a genetic program pertaining to stem cells has been activated. Otherwise, the latter is switched off after the development of the embryo under normal circumstances. However, certain cells have crestin and other genes in the program turned back on for reasons unknown.
The fish were observed for fluorescence. The researchers note that they would see a green spot on a fish very often. These would ultimately become tumours.
Kaufman and his team eventually discovered that crestin and the other genes that were also activated were the same ones that were turned on during the development of zebrafish embryo in their stem cells that would turn into pigment cells. Another author, Leonard Zon, describes this as a “change in cell fate”.
Given the similarity of the rarity of the events where cells become melanoma in humans and fish, the authors think that the basis of melanoma formation might be same in humans too.
The authors believe that their findings might pave the way for the development of a genetic test that would identify cells behaving like the pigment cells which would be an indication of the activation of the stem-cell program.
Furthermore, Kaufman and his team have brought forth a new model for the formation of cancer. According to their theory, normal tissues become primed for cancer upon the activation of oncogenes and the loss of tumour suppressor genes. However, that cancer will only form when a cell in that tissue goes back to the embryonic state whereby cell division occurs.