Paper published in PNAS reports that Lefty silences Nodal, which is essential for hESC pluripotency and is overexpressed in cancers.

A protein that governs development of human embryonic stem cells (hESCs) also inhibits the growth and spread of malignant melanoma, Northwestern University researchers discovered. They additionally found that the protein, called Lefty, prevents aggressive breast cancer cells from metastasizing.

In previous experiments, the investigators found that aggressive melanoma and breast cancer produce a morphogenic protein called Nodal, which is essential for hESC pluripotency.

In this study, the team found that the Lefty protein inhibits production of Nodal and therefore plays a role in normal embryonic cell differentiation and development. They also discovered that metastatic tumor cells do not express Lefty, allowing them to overproduce Nodal in an unregulated manner.

When the group exposed metastatic tumor cells to the microenvironment of hESCs containing Lefty, they say there was a dramatic reduction in Nodal expression in these cancer cells. They also noted a decreased tumor cell growth and invasiveness and an increase in apoptosis. Although exposure to a hESC microenvironment inhibited Nodal expression and tumor growth in both metastatic melanoma and breast cancer cells, melanoma cells responded to Lefty within three days, but breast cancer cells required two additional days to achieve the most significant reduction in Nodal, according to the ivnestigators.

While findings from the study suggest that hESC-derived Lefty may have the potential to prevent metastasis, observations from the study highlight the potential utility of isolating other factors within the hESC microenvironment responsible for influencing tumor cell fate and reversing the cancerous properties of metastatic tumor cells.

Results of the study were described in an article in the March 3 online version of the Proceedings of the National Academy of Sciences.

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