Brain Cytokine Inhibits Cancer Spread While Protecting Neurons

Cancers that have spread to the brain have decreased pigment epithelium–derived factor (PEDF) activity, which may be linked to the poor prognosis for patients in this condition.

Previous studies have found that the cytokine PEDF was downregulated in resected human brain metastases of breast cancer compared with primary breast tumors, suggesting that restoring its expression might limit metastatic spread.

PEDF is a member of the serpin family, although it does not display the serine protease-inhibitory activity shown by many of the other serpin family members. The protein is secreted and it strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells.

Investigators at the [US] National Cancer Institute (Bethesda, MD, USA) performed in vitro analyses as well as direct intracranial implantation in a mouse model to study metastasis of breast cancer tumors into the brain.

They reported in the January 1, 2012, issue of the journal Cancer Research that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression. The suppressive effects of PEDF were not only rapid but also independent of the effects of this factor on angiogenesis. Paralleling its cytotoxic effects on breast cancer cells, PEDF also exerted a prosurvival effect on neurons that shielded the brain from tumor-induced damage, as indicated by a relative 3.5-fold reduction in the number of dying neurons adjacent to tumors expressing PEDF.

PEDF is currently being studied as a therapy for macular degeneration because it has been shown to protect neurons in the retina. The potential value of PEDF in cancer therapy remains to be evaluated. “We are making progress from the neck down in cancer treatment, but brain metastases are increasing and are often a primary reason patients with breast cancer do not survive,” said senior author Dr. Patricia S. Steeg, head of the women's cancers section at the [US] National Cancer Institute.

Related Links:
National Cancer Institute