Stem Cell Microenvironment Tames Malignant Cells

Cancer researchers have found that the microenvironment maintained by human embryonic stem cells (hESCs) contains factors that can inhibit the growth and spread of malignant cancers such as melanoma and breast cancer.

Previous studies had shown that aggressive melanoma and breast carcinoma express the embryonic morphogen Nodal, which is essential for human embryonic stem cell (hESC) pluripotency (the ability to differentiate into different types of mature cells). A morphogen is a signaling molecule that acts directly on cells (not through serial induction) to produce specific cellular responses dependent on morphogen concentration.

In the current study published in the March 11, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences, investigators at Northwestern University (Evanston, IL, USA) found that hESCs produce an inhibitor of Nodal called Lefty. Metastatic tumor cells do not express Lefty, allowing them to overexpress this embryonic morphogen in an unregulated manner. However, exposure of the tumor cells to a hESC microenvironment (containing Lefty) led to a dramatic down-regulation in their Nodal expression, which coincided with a reduction in clonogenicity and tumorigenesis accompanied by an increase in apoptosis.

Lefty was found to be secreted only in hESCs and not in any other stem cell type tested – including stem cells isolated from amniotic fluid, cord blood, or adult bone marrow – or placental cells.

"This observation allowed us to appreciate the powerful influence of the hESC microenvironment on the reprogramming of metastatic melanoma cells,” said senior author Dr. Mary J. C. Hendrix, professor of cancer research at Northwestern University. "Further, the tumor suppressive effects of the hECs microenvironment, by neutralizing the expression of Nodal in aggressive tumor cells, provide previously unexplored novel therapeutic modalities for cancer treatment.


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