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Reversing cancer cells to normal cells

he melanoma cells are sending and receiving, Dr. Hendrix and her colleagues used the microenvironment of the zebrafish to study whether the tumor cells could communicate with the zebrafish stem cells and affect their early development. The zebrafish is a widely-used organism for genetic and developmental studies because of its prolific reproduction, rapid development, and transparent embryo that develops outside the body (making it especially easy to simply watch development), and the fact it develops organs and tissues comparable to those in humans, such as heart, kidney, pancreas, bones and cartilage.)

Using the zebrafish model, and the extraordinary technologic advances made in microscopy and molecular biology in recent years, the team was able to show that the aggressive melanoma cells secrete Nodal, a critical component underling the two-way communication between tumor cells and the embryonic microenvironment. Nodal is an embryonic factor (also called a morphogen) responsible for maintaining the pluripotency of human embryonic stem cells: their ability to develop or "morph" into one of a variety of body cells. When aggressive melanoma and other tumor cells (recent findings also report Nodal expression in breast cancer and testicular cancer) regain the ability to express a potent embryonic morphogen like Nodal, the presence of the Nodal and the signals it sends and receives appear to play a key role in tumor cell plasticity and progression.

Most noteworthy, Dr. Hendrix’s team’s also has shown that inhibition of Nodal signaling leads to a reduction in melanoma cell invasiveness and ability to create new tumors. In fact, with inhibition of Nodal, the metastatic melanoma cells are reverted to a more benign skin cell without the ability to form tumors.

Findings from the zebrafish study were further confirmed in the human embryonic stem cell model and the chick embryo model - where inhibiting Nodal signaling led to the reversal of
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Source:Northwestern University


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