Switch of carcinogenesis

When a benign tumor becomes malignant

Kirill Stasevich, "Science and Life"

The transformation of a "good" tumor into a "bad" one is accompanied by the inclusion of molecular signals that encourage some cells to multiply with a vengeance.

We know that tumors can be malignant and benign. A benign tumor is the same uncontrollably dividing cells, but with important differences: firstly, such a tumor grows slowly, it does not metastasize, it can be removed without problems, and relapses after that happen quite rarely; secondly, although it squeezes the surrounding tissues, it does not germinate in them. 

Finally, the cells in it differentiate as they should, that is, they acquire characteristic tissue functions – in other words, such a tumor is structurally similar to an overgrown specialized epithelium or muscle. (One of the most famous examples of a benign tumor is prostate adenoma.) 

However, a benign tumor can become malignant. In an article in Nature, A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma, Tuomas Tammela and his colleagues from The Massachusetts Institute of Technology writes how pulmonary adenocarcinoma – one of the most aggressive and common lung tumors – can arise from benign adenomas. 

The researchers were engaged in the Wnt signaling pathway – this is the name of the system of signaling proteins on which embryonic development and tissue regeneration depend. The essence of Wnt signals is to keep cells in a stem state so that they do not stop dividing. 

It is clear why the Wnt pathway works during embryogenesis: the embryo needs a lot of cellular material to form tissues and organs. It is clear why the Wnt pathway works where there is a constant active loss of cells, for example, in the intestine: if all stem cells stop dividing here and turn into specialized cells of the intestinal epithelium, then problems will soon begin with the intestine. 

And it is also clear that incorrectly working Wnt proteins can cause a tumor. The fact that the Wnt pathway plays an active role in some oncological diseases has been known for a relatively long time, but the authors of the work were interested in lung tumors. 

Experiments were conducted with mice whose pulmonary adenoma turned into adenocarcinoma. It turned out that in a benign tumor, Wnt proteins were silent, but during the transformation, Wnt signals began to work - not in all cells, only 5-10%, but they became a constant source of new and new cancer cells. 

At the same time, other cells of a benign tumor created a special microenvironment in which cells with active Wnt signals could exist and divide. If there were no such microenvironment, their stem properties, their ability to infinite division would quickly fade away. 

A degenerating lung tumor. Cells in which Wnt signals are activated,
painted green. (Tuomas Tammela, Biologists identify key step in lung cancer evolution).

So, the transformation of a benign pulmonary adenoma into a malignant adenocarcinoma occurred as follows: in a small part of the tumor cells, the Wnt signaling pathway was activated, prompting them to divide even faster and more aggressively, and at the same time these cells received a convenient environment that supported them in a new, malignant state. 

When the researchers gave mice substances that inhibit the activity of Wnt proteins, the tumors stopped growing, and the animals lived one and a half times longer. (The experiments used a drug that acts on all nineteen Wnt proteins and which is currently undergoing clinical trials.) 

According to the authors of the work, people with pulmonary adenocarcinoma in 70% of cases have cells in the tumor with a working Wnt pathway, and in 80% of cases, you can find the same niches with a microenvironment that favors the launch of Wnt signals. 

Most likely, adenocarcinomas in the lungs develop like this – from benign neoplasms that rapidly degenerate into cancer. Perhaps, using drugs that disable Wnt signals, we can at least somehow tame, even if not all, but at least some types of cancer. 

Portal "Eternal youth" http://vechnayamolodost.ru  15.05.2017