Inhibition of Nodal Prevents Melanoma Metastasis and Growth
The protein, which maintains pluripotency in stem cells, is used in signaling for melanoma and other cancers.
Aggressive melanoma cells express a protein that when inhibited, reduces invasiveness and reproduction, according to Northwestern University scientists. These results were seen in zebrafish, human embryonic stem cells, and chick embryo models.
The researchers used the zebrafish to study whether the tumor cells could communicate with stem cells and affect their early development. They showed that the aggressive melanoma cells secrete the protein nodal that underlies the two-way communication between tumor cells and the embryonic microenvironment.
Nodal is an embryonic factor, or morphogen, responsible for maintaining the pluripotency of human embryonic stem 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, its presence and the signals it sends and receives appear to play a key role in tumor cell plasticity and progression.
The team also showed that inhibition of nodal signaling leads to a reduction in melanoma cell invasiveness and ability to create new tumors. In fact, with inhibition, 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 a human embryonic stem cell model and a chick embryo model.
The results were presented at the American Association of Anatomists’ plenary lecture and symposium, at “Experimental Biology 2007” in Washington, D.C.