The initiation of cancer cells has been observed for the first time, together with the rebirth of certain cell states only usually seen during embryonic development. Using zebrafish to model how this process is initiated, it implicated progenitor cells and an improbable reactivation.
Observing the initiation of cancerous cells seems to have been a challenging task in the past; this may be due to the rarity of these events and a corollary; the small probability of witnessing them. Present research aims to use certain model organisms to overcome this where the processes may be clearly observed and to then observe the initiation of cancer. New directions have developed as a consequence of these previously undetected mechanisms and the endeavour may now result in new explanations of cancer.
One of the current explanations of cancer, may be the relation these events have to the nature of stem cells and progenitor cells. Stem cells are cells which may differentiate into any type of cell, whereas progenitor cells are usually more functionally specific and only active in embryonic development. These types of cells have been seen to play a major role in the commencement of cancerous cells, when stem or progenitor cells are reawakened and have a brief spell of vulnerability.
Some cells in the human body have mutations associated with cancer yet avert full development into cancer, why this occurs has intrigued scientists. The concept of “field cancerisation” where large areas of any tissue or organ may be affected by alterations, —sometimes involving molecular lesions —, may result in genetic and epigenetic mutations which occur over a large “field”. These initial stages develop from precancerous or aberrant cells to cancerous cells. These fields have been shown to have reduced DNA repair enzymes and this is therefore a signal of potential progression to cancer. How enzymes recycle impaired cells is a key mechanism in cancer development, when cells senesce, this mechanism is impeded averting the necessary healthy redevelopment particularly in ageing individuals.
This week a new study by Kaufman and his colleagues at the Boston Children’s hospital, used zebrafish (a model organism) to observe the development of cancer. The fish had a specific cancer mutation and also had an absent tumour suppressor gene. The fish were engineered so a fluorescent light would turn green if a crestin gene was activated, this showed the genetic initiation of stem cells. This genetic program is deactivated usually post embryonic development although reactivated in certain cells under specific conditions.
The results indicated when these genes were turned on it resulted in tumours 100% of the time, a perfect outcome seen infrequently in science. The team demonstrated how cancer initiates after the switching on of an oncogene or absence of a tumour suppressor and the consequences are a return for single cells to a stem cell state. The genes are activated during embryonic development in melanocyte stem cells (skin pigment) within a structure called the neural crest which develops originally from the outer layer of the skin; the ectoderm. It is the same gene activated during human cancer initiation.
The findings demonstrate how tissue maybe vulnerable to cancerous alterations when these oncogenes are activated and tumour suppressor genes are silenced. However, another factor is needed; a cell reverting to a stem cell state which starts proliferating. Modifications due to super enhancers increase the transcription of particular genes, this emphasises how an epigenetic mechanism of cancer may exist, moreover, the overexpression of crestin genes in these melanocytes actually accelerated melanoma development. The neural crest progenitor state reactivation last seen in embryonic development is therefore a key event in cancer initiation. It may be a significant biomarker of the condition and the team suggest the findings may lead to a genetic test capable of detecting when a cancer program has been initiated.
This may lead to the possibility of abating the development of cancer relieving many from the condition and aiding the health services despite this the productive news is; many are now living much longer after a diagnosis and treatment and have an improved quality of life.
What might be an improved way to impede the development of cancer?