In previous work, the researcher Mary JC Hendrix and colleagues discovered that aggressive melanoma cells (as opposed to normal cells and less aggressive melanoma) contain specific proteins similar to those found in embryonic cells. This work allows a first molecular classification of malignant melanoma and may help explain how behaving like unspecialized stem cells, melanoma cells migrate, invade and metastasize while virtually unnoticed by the immune system.
Now, a new work, Dr. Hendrix describes new research that used an innovative experimental approach to study precisely how you can transform human metastatic melanoma cells to normal-like skin cells – by exposing the microenvironment of human embryonic cells.
The plenary lecture by Dr. Hendrix on April 29 was characterized as “a ray of light” by the American Association of Anatomists. His presentation is titled “convergence of embryonic and tumor molecular pathways: their role in tumor plasticity.” Plasticity refers to the ability of tumor cells, including embryonic stem cells, to differentiate into various cell types. During cancer progression, malignant cells receive and send signals of their own microenvironment, growth signals that promote tumor metastasis. To better understand what signals are sent and received melanoma cells, Dr. Hendrix and his colleagues used the microenvironment of the zebrafish to study whether tumor cells could communicate with stem cells and affect their early development. The zebrafish is a widely used organism for genetic studies and development because of its prolific reproduction, rapid development, and transparent embryo, and the fact that it develops organs and tissues comparable to humans, such as heart, kidney, pancreas , bones and cartilage.
Using the zebrafish model, and extraordinary techniques of microscopy and molecular biology, the team was able to demonstrate that aggressive melanoma cells produce a critical component for communication between tumor cells and embryonic microenvironment. Nodal is an embryonic factor responsible for maintaining the capacity of division of stem cells and their ability to become a variety of tissues. When aggressive melanoma and other tumor cells (recent findings also describe the expression of this factor in breast cancer and testicular cancer) regain the ability to express a potent embryonic morphogen like Nodal, the presence of nodal and signals; and receives appear to play a dominant role in plasticity and tumor progression.
The team of Dr. Hendrix also demonstrated that inhibition of Nodal leads to a reduction in the invasiveness of melanoma cells and their ability to create new tumors. In fact, the inhibition of nodal metastatic melanoma cells become benign cells of skin without ability to form tumors. The results of the study in zebrafish were further confirmed in a model human embryonic stem cells and in a chick embryo model, where inhibiting Nodal signaling was obtained by an equivalence transformation of melanoma cells in normal cells.
“This is a promising research field,” says Dr. Hendrix. The discovery of a new signaling pathway in melanoma and other tumor cells and the ability to inhibit Nodal and thus induce the transformation of melanoma cells in normal skin cell provide a previously unknown target for progression and metastasis tumor.