Release date: 2017-08-16
Epithelial cells covering the surface of human skin and various lumens (esophagus, stomach, intestine and trachea, etc.) are the main sites of malignant tumors. Two important reasons are: epithelial cell division is active and epithelial cells Affected by the surrounding environment, this also leads to a higher probability of genetic mutations in epithelial cells.
How high is it?
In 2015, scientists at the Sanger Institute in Cambridge, England, obtained normal skin tissue from the eyelids of the elderly who underwent orbital plastic surgery. They then listed 74 important oncogenes and targeted ultra-deep sequencing.
The eyelids of the elderly used by scientists at the Sanger Institute in Cambridge, UK (a glance at the glance)
The result is even more shocking than the above picture. Skin tissues that do not seem to have any pathological changes are actually not as healthy. 18-32% of the cells carry oncogene mutations, and an average of about 140 carcinogenic drive mutations can be found per square centimeter of epithelial tissue. Their important discovery was published in the journal Science [1]!
Cellular oncogene mutations in 1 square centimeter of skin, many cells carry multiple mutations
Be aware that the above 74 genes are all oncogenes, either they will make the cells grow wildly or they will promote tumor formation. However, what puzzles scientists is that these organizations are not cancerous or even have any visible tissue abnormalities.
Why do tissues carrying a large number of oncogene mutations do not have a tumor? Why did the set of tumors suddenly fail?
Dr. Valentina Greco of Yale University and Dr. Slobdan Beronja of the Fred Hutchinson Cancer Research Center have been thinking about this issue. In their view, the solution is to see for yourself what the cells carrying the mutation are.
Dr. Valentina Greco (left) and Dr. Slobodan Beronja (right)
For the convenience of observation, they chose hair follicle stem cells in the skin of mice as subjects. Dr. Greco and Dr. Beronja first genetically engineered a small fraction of the hair follicle stem cells in the resting skin of mice, allowing the β-catenin gene to control cell growth, so that these cells acquire the ability to rapidly divide and proliferate. This is the necessary ability to form a tumor.
They then observed the skin of the mouse under a two-photon microscope. As a result, they found that cells with mutations in the β-catenin gene caused the production of neoplasms within 1 to 2 weeks, but 80% of the neoplasms regressed within 4 weeks and did not rebound in the following weeks. What is even more shocking is that even the 20% of the creatures that have not subsided will completely disappear during the rest of the skin!
This is strange.
Next, Dr. Greco and Dr. Beronja labeled the mutant cells and normal cells with red fluorescent protein and green fluorescent protein, respectively, to track the behavior of cells in the growth phase and regression phase of hair follicles.
As a result, they found that in the growing season, those cells with mutations are located in the middle of the neoplasm. Before the degenerative phase, normal cells are distributed around the cells of the genetic mutation, and these mutant cells are surrounded, and the red cells carrying the genetic mutation are gradually eliminated.
In the beginning, the mutant cells (red) grow faster and try to break through. As time goes by, normal cells (green) grow faster and form a close-up, and the mutant cells are cofferent (or successfully modified).
The mutation of the gene (red) is a deadly breakout, and the result is not surrounded by normal cells (green).
Is normal cells really coercing cells with genetic mutations? Therefore, the researchers used genetic modification technology to reduce the number of normal cells around the mouse mutant cells. After a reduction in the number of normal cells, only 40% of the neoplasms regressed, and others grew.
Immediately afterwards, the researchers genetically engineered normal cells to fail to proliferate at all. As a result, less than 2% of the neoplasms have subsided. This means that normal cells are necessary for the elimination of mutant cells in tissues!
After the normal cells (green) no longer proliferate, the mutant cells (red) grow freely
After normal cells (green) cannot proliferate, the mutant cells (red) are out of control!
Dr. Beronja said with excitement: "This is an unexpected repair mechanism! Your skin can tolerate carcinogenic mutations by actively removing mutant cells!"[2]
Recently, this important discovery by Dr. Greco and Dr. Beronja was published in Nature [3]. This study tells us that when skin cells containing oncogenic mutations begin to form tumors, adjacent normal skin cells will actively correct tissue defects caused by abnormal cells, just like the police who punish the good! Specifically, normal skin cells surround the deformed tissue, either destroying these neoplastic tissues or transforming them into normal skin structures including hair follicles!
Yes, skin cells carrying oncogenic mutations are rounded up by normal cells, modified, or encircled! What's more interesting is that normal cells will not stay in place after they have finished their work, but they will leave when they are finished, or they will go while doing it. This will prevent the formation of neoplasms.
The arrow refers to the normal cells that are left to work.
So is this phenomenon unique to hair follicle stem cells, and other cells do not exist? Or is this phenomenon only for the beta-catenin signaling pathway? In the same way, the researchers observed similar phenomena in stem cells between hair follicles and other genetic mutations.
Schematic diagram of normal cells (green) containing genetically modified cells (red),
Normal cells enclose the mutant cells while organizing and disciplined autophagy.
Or evacuate the scene
Does this phenomenon still exist if multiple cells are mutated at the same time? They mutated several cells, which proved to cause skin tumors. As a result, at the 3rd week after the induction of the mutation, the skin of the mouse did have a tumor and the face was deformed (see the figure below).
However, in the fourth month, the tumor of the mouse disappeared and the skin returned to normal. Of course, there will still be hair follicles and sebaceous gland structures. This suggests that the skin epithelium can eliminate abnormal structures, regardless of their size, to re-establish normal tissue structure and function.
Although there will be discomfort, it is recommended to look closely and look closely. After a variety of cell mutations, the tumor surface deformed in the mouse at 3 weeks (left), but the mouse's face returned to normal at 4 months.
Dr. Greco and Dr. Beronja's research shows that in the face of constant attacks initiated by abnormal cells, the skin has formed a mechanism to deal with these provocations, trying to kill the tumor in the cradle! [2]
Currently, researchers are investigating other active tissues, such as oral mucosal cells, as well as inactive tissues, such as breast ducts of breast ducts; to understand whether the anti-cancer mechanisms that maintain normal tissue status are related to cell transfer characteristics, rather than Cell type related.
They are also gaining insight into the specific signals involved in anticancer mechanisms, exploring how these signals work, and how they can lead to tumor growth after an error. We hope that this research results can be transformed into clinical applications as soon as possible, providing new ideas for cancer prevention and treatment!
Reference material
[1] Martincorena I, Roshan A, Gerstung M, et al. High burden and pervasive positive selection of somatic mutations in normal human skin [J]. Science, 2015, 348(6237): 880-886.
[2]https://
[3] Brown S, Pineda CM, Xin T, et al. Correction of aberrant growth preserves tissue homeostasis [J]. Nature, 2017.
Source: Singularity Network (micro signal geekheal_com)
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