Embryonic stem Cell Protein Suppresses tumor Growth
In an earlier work, scientists at Northwestern University (Evanston, Illinois), working under the guidance of Professor Mary J.C. Hendrix, found that the Lefty protein, which controls the development of human embryonic stem cells, suppresses the growth and metastasis of melanoma, the most dangerous type of skin cancer. The results of the authors' latest study showed that this protein also prevents the metastasis of aggressive breast tumors. An important point is that the Lefty protein synthesized by embryonic stem cells is no longer secreted by any of the tested types of stem cells, including amniotic fluid cells, umbilical cord blood and bone marrow.
Embryonic stem cells, depending on the signals they receive from the microenvironment (surrounding cells, tissues, vessels), can turn into cells of more than 200 types found in an adult organism. During the development of a malignant tumor, its cells also receive signals from the microenvironment that stimulate tumor growth and metastasis.
The results of the work shed light on the processes leading to the fact that malignant cells become similar to non-specialized stem cells, invisible to the immune system, but having the ability to move around the body and infiltrate healthy tissues.
Previously, the authors demonstrated that a three-dimensional matrix containing signaling proteins produced by human embryonic stem cells induces the transformation of malignant melanoma cells into normal cells resembling skin cells and capable of forming colonies similar to those of embryonic stem cells.
In subsequent experiments, the scientists found that aggressive melanomas and breast tumors synthesize the morphogenic Nodal protein, which provides pluripotency of embryonic stem cells. Another group of researchers found this protein in testicular cancer tumors. Based on these results, Nodal protein was recognized as a prognostic marker of aggressive behavior of tumors.
The results of the latest work showed that Lefty protein suppresses Nodal protein synthesis and, therefore, plays an important role in the differentiation and development of embryonic stem cells under normal conditions. At the same time, metastatic tumor cells do not express the Lefty protein, which leads to uncontrolled Nodal hyperproduction.
When metastatic cells were placed in an embryonic stem cell culture medium containing Lefty protein, Nodal protein synthesis was significantly reduced in tumor cells, while cell growth slowed down and their invasiveness decreased with a simultaneous increase in the level of apoptosis (programmed cell death).
Exposure to the microenvironment of embryonic stem cells inhibited Nodal expression and suppressed the growth of both metastatic melanoma and breast cancer. However, breast cancer cells underwent more complex reprogramming. The effect of factors released by embryonic stem cells on melanoma cells reached a maximum within two days, and on breast cancer cells – within 5 days. Apparently, this is due to differences in the signaling mechanisms involved, which, however, in both cases lead to the launch of the process of self-destruction of cells.
The uniformity of the results of the reactions of the two types of cancer is due to the characteristics that ensure the similarity of highly aggressive tumor cells, regardless of their original belonging to a particular tissue.
The authors claim that the antitumor effect of the microenvironment of embryonic stem cells, mediated by the suppression of Nodal protein expression in aggressive cancer cells, opens up new opportunities in cancer treatment. Moreover, they believe that Lefty protein is not the only factor secreted by embryonic cells that has an antitumor effect.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily 13.03.2008