"Genes of metastases"
A group of bioengineers and bioinformatics from the University of California at San Diego has discovered a complex of genes that determines the ability of a tumor to metastasize.
The metastatic spread of the tumor throughout the body is the cause of 90% of deaths associated with oncological diseases. Modern methods of treatment, such as chemotherapy and radiation therapy, are able to suppress the growth of metastases, but they are very difficult to tolerate by patients and are associated with a high risk of complications. In these conditions, the search for mechanisms of tumor spread and ways to prevent it is of great importance.
To study the processes that trigger the spread of tumor cells throughout the body, the researchers placed cancer cells in a specially designed three-dimensional collagen matrix. They found that tumor cells turn into structures that mimic blood vessels, consisting of short fibers and small pores.
A breast tumor cell placed in a dense matrix. On the seventh day, imitation of angiogenesis (vascular mimicry-like behavior) began – the growth of vascular structures with nuclei (blue) and cytoskeleton (green).
The behavior of cancer cells did not depend on the properties of the matrix, including density, oxygen saturation and stiffness. This surprised scientists: they assumed that the introduction of tumor cells into a denser environment would stop the processes of metastasis. In traditional Petri dishes, tumor cells did not show such activity. This proves that in order to fully study the properties of cancer cells in vitro, they must be placed in a three-dimensional environment as close as possible to natural conditions.
An in vitro study describes the process of imitation of angiogenesis – the growth of structures resembling vessels in aggressive forms of cancer: their inner wall is lined not with endotheliocytes, but with tumor cells.
Vascular-like structures are actively involved in the blood supply of the tumor and carry out communication between cells of different localization. This contributes to the malignant growth and metastasis of cancer. What exactly triggers "pseudoangiogenesis" remained unknown.
A set of genes called collagen-induced network phenotype (CINP) has been discovered, which determines the behavior of cancer cells and activates the process of imitation of angiogenesis.
A network of cells was stained to detect membrane proteins. The positive result testified to the similarity with the vessels and proved the presence of imitation of angiogenesis.
The researchers then used oncological histological databases to search for CINP in nine types of tumor cells, including breast, lung, kidney and pancreatic cancers. The study showed that the presence of the CINP module correlated with the degree of malignancy and aggressiveness of the tumor.
Thus, the determination of CINP in cancer patients is able to predict their life expectancy and the likelihood of tumor metastasis. This gene module can be used as a marker of cancer malignancy and help in choosing the appropriate treatment method.
Further steps in this direction are to conduct preclinical studies on animals. In addition, it is necessary to continue studying the mechanisms of metastasis and develop ways to block the transformation of healthy cells surrounding the tumor into vascular-like structures.
The article by D.O.Velez et al. 3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from UC San Diego: Researchers discover specific tumor environment that triggers cells to metastasize.