Stop metastases at the border

In experiments on mice, the first stage was successfully blocked
metastasis of breast cancer

NanoNewsNet based on Johns Hopkins Medicine: First Step of Metastasis Halted in Mice with Breast CancerCell biologists from The Johns Hopkins University School of Medicine have discovered a unique class of breast cancer cells that control the process of invasion of a cancerous tumor into the surrounding tissues.

Since invasion is the first stage of the metastasis process, scientists may have found a weak link in the defense of this deadly disease and a new therapeutic target. The results of the study are published online in the journal Cell (Cheung et al., Collective Invasion in Breast Cancer Requires a Conserved Basal Epithelial Program).

"Metastases are the biggest threat to breast cancer patients, and we found a way to stop the first part of this process in mice," says study leader Andrew Ewald, PhD, associate professor of cell biology at the School of Medicine.

Before the onset of metastasis, individual cells on the border of the tumor, called the leader, or leading, form outgrowths that penetrate into the surrounding tissues. If the conditions assessed by them turn out to be suitable, the leader cells act as conductors: after them, invading healthy tissue, many other cancer cells leave the tumor limits. Metastasis as such can be said if the cell has managed to migrate to another organ, for example, to the lungs, and form a new tumor there.

Starting with the idea of increased aggressiveness of some cancer cells, Dr. Ewald and his colleagues grew mouse tumors in special 3-D gels that mimic the environment surrounding breast tumors in the body of sick people. Kevin Cheung, MD, an employee of the Ewald laboratory, noticed that cancer cells penetrated the gel in groups, with several cells in front and the rest following them.

In an effort to understand the molecular causes of the apparent "leadership" of the initiator cells, Dr. Ching searched for proteins present only in the leader cells. He identified the protein cytokeratin 14 (cytokeratin 14), or K14, produced by almost all leader cells, but very rarely found in non-invasive parts of the tumor.

Protein K14 participates in the formation of the internal skeleton of cells of many types, giving them a certain structure, and also ensures their mobility.

As further experiments have shown, K14-containing leader cells are widely represented in other types of mouse breast cancer, regardless of how predisposed these tumors are to invasion. But the more invasive the tumor, the more cells with K14 in it.

Diagram from the article in the Cell – VM

After repeating experiments on the tumors of 10 breast cancer patients, the scientists came to the same conclusion: the leader cells of these human tumors also synthesize K14.

"Our study shows that the most aggressive breast tumor cells express K14 in all types of breast cancer," comments Dr. Ching. "Now we need to find out how to remove these leader cells from patients' breast tumors."

The presence of K14 in the leader cells presented its participation in the invasion process as more than likely, but the researchers still decided to conduct additional experiments and make sure that it was not a simple coincidence.

They divided the tumors removed from mice with breast cancer into experimental and control groups. Both groups of tumors were exposed to viruses that delivered fragments of genetic material to the cells. Genetic information preventing the synthesis of K14 was introduced into the experimental group; in the control group, it had no effect on the cells. Then both groups of tumors were transplanted to healthy mice – an experimental tumor was transplanted to one side of the animal, and a control tumor was transplanted to the other.

After some time, the tumors were removed and studied. As expected, the control group had leader cells containing K14, the conductors of active tumor invasion into normal tissue. The boundaries of the experimental tumors, in the cells of which there was no K14, were smooth, and there was practically no invasion.

"It will take several more years of research before we can use this knowledge to help breast cancer patients, but now we know which of the tumor cells are most dangerous, and we know some of the proteins they rely on in their dirty business," says Dr. Ewald. "Just a few leader cells are enough to start the metastasis process, and they need K14 to lead this invasion."

Protein K14, the scientist notes, is present in the cells of many organs and, therefore, may play a similar role in the development of other types of cancer.

Portal "Eternal youth" http://vechnayamolodost.ru30.12.2013