American Association for Cancer Research
00085472can111904-sup-f1_954k.pdf (954.19 kB)

Supplementary Figure 1 from Opposing Effects of Pigment Epithelium–Derived Factor on Breast Cancer Cell versus Neuronal Survival: Implication for Brain Metastasis and Metastasis-Induced Brain Damage

Download (954.19 kB)
journal contribution
posted on 2023-03-30, 21:02 authored by Daniel P. Fitzgerald, Preeti Subramanian, Monika Deshpande, Christian Graves, Ira Gordon, Yongzhen Qian, Yeva Snitkovsky, David J. Liewehr, Seth M. Steinberg, José D. Paltán-Ortiz, Mary M. Herman, Kevin Camphausen, Diane Palmieri, S. Patricia Becerra, Patricia S. Steeg

PDF file - 954K



Brain metastases are a significant cause of morbidity and mortality for patients with cancer, yet preventative and therapeutic options remain an unmet need. The cytokine pigment epithelium–derived factor (PEDF) is downregulated in resected human brain metastases of breast cancer compared with primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here, we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression, as supported by in vitro analyses as well as direct intracranial implantation. Notably, the suppressive effects of PEDF were not only rapid but 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. Our findings establish PEDF as both a metastatic suppressor and a neuroprotectant in the brain, highlighting its role as a double agent in limiting brain metastasis and its local consequences. Cancer Res; 72(1); 144–53. ©2012 AACR.