Stem Cell Protein Promotes Formation of New Blood Vessels in Aggressive Breast Cancer

A protein that functions in the developing embryo and is characteristic of embryonic stem cells (ESCs) has been found also to be active in an aggressive form of breast cancer where it promotes development of new blood vessels for the rapidly growing tumor.

Investigators at the University of Western Ontario (London, Canada) focused their research on the Nodal protein. Nodal is a member of the TGF-beta protein superfamily. Studies of the mouse counterpart of this protein have suggested that this protein may be essential for mesoderm formation and subsequent organization of axial structures in early embryonic development. Nodal does not function in mature normal cells.

The investigators reported in the August 1, 2012, online edition of the journal Cancer Research that high levels of Nodal positively correlated with high vascular densities in human breast lesions. In vitro, Nodal facilitated breast cancer–induced endothelial cell migration and tube formation, largely by upregulating the expression and secretion of factors that promoted formation of new blood vessels by the breast cancer cells. Results of a directed in vivo angiogenesis assay and a chick chorioallantoic membrane assay showed that Nodal promoted vascular recruitment in vivo.

By using genomic techniques to inhibit Nodal expression following tumor formation in a mouse breast cancer model, the investigators induced significant reduction in tumor vascularization together with elevated hypoxia and tumor necrosis.

"We have determined that breast cancers, specifically those very aggressive, invasive breast cancers that spread, express an embryonic protein called Nodal and the expression of this protein is correlated with more blood vessels in the tumor. Blood vessels, many studies have shown, help to allow tumors to grow but also to spread throughout the body," said senior author Dr. Lynne-Marie Postovit, professor of anatomy and cell biology at the University of Western Ontario. "In addition, we have shown that if we can target this embryonic protein, we can cause the blood vessels to collapse within the tumor, leading to decreased oxygen levels and tumor cell death. When tumors lack oxygen and nutrients they become what we call necrotic."

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