Growth factor-promoting angiogenesis expressed in tumor cells and normal neurons

Scientists have discovered that a stem cell factor overexpressed both in brain tumor cells and in neurons following brain injury promotes tumor survival by inducing angiogenesis. The research study, published in the April issue of Cancer Cell, examines the interaction between tumor cells and surrounding tissues and may have substantial significance for design of more effective therapeutics for one of the most lethal types of tumor, malignant gliomas.

Stem cell factor (SCF) is an important growth factor for multiple cell types. Research has shown that SCF is expressed in glioma cells and as a result of various types of brain injury, but its significance is not fully understood. Dr. Howard A. Fine from the National Cancer Institute/National Institute of Neurological Disorders and Stroke at the National Institutes of Health and colleagues designed a study to investigate whether, as a result of tumor-induced brain injury, brain cell-mediated SCF expression contributes to tumor growth by setting up an environment that supports angiogenesis and tumor progression.

The researchers demonstrate that decreased SCF expression in vivo results in decreased angiogenesis and improved survival in mouse glioma models, whereas overexpression of SCF is associated with a worse prognosis and shorter survival in patients with glioblastomas. SCF expression is not directly linked to tumor cell proliferation but instead encourages the growth of blood vessels needed to support the expanding tumor. Importantly, these findings provide definitive evidence that factors promoting tumor progression extend beyond the tumor itself and involve a complex interaction between the cancer cells and the normal cells that are perturbed by expanding tumor.

These results suggest that SCF is a potent glioma-associated angiogenic factor that plays a prominent role in pathological angiogenesis both through direct tumor cell expression of SCF and by normal neurons that are damaged by the growing tumor. The researchers point out that the clinical significance of these findings extends beyond identification of SCF as a rational target for gliomas. "Normal neuronal expression of SCF in response to traumatic brain injury also raises the disturbing possibility that standard invasive procedures such as surgical biopsies or partial tumor resections may be inducing a proangiogenic response, or trigger, within the brain," cautions Dr. Fine.

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Lixin Sun, Ai-Min Hui, Qin Su, Yuri Kotliarov, Sandra Pastorino, Jennifer Walling, Rolando Bailey, and Howard A. Fine of the National Cancer Institute/National Institute of Neurological Disorders and Stroke, National Institutes of Health in Bethesda, MD; Alexander Vortmeyer of the National Institute of Neurological Disorders and Stroke, National Institutes of Health in Bethesda, MD; Antonino Passaniti of the University of Maryland School of Medicine in Baltimore, MD; Jayant Menon of the National Institute of Neurological Disorders and Stroke, National Institutes of Health in Bethesda, MD and Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program in Bethesda, MA; Marc Rosenblum and Tom Mikkelsen of Henry Ford Hospital in Detroit, MI. J.M. was a 2004 HHMI-NIH Research Scholar.

Sun et al.: "Neuronal and Glioma-Derived Stem Cell Factor Induces Angiogenesis within the Brain." Publishing in Cancer Cell 9, 287–300, APRIL 2006. DOI 10.1016/j.ccr.2006.03.003 www.cancercell.org


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