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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Vaidehi, Nagarajan Roberts, Eugene Jandial, Rahul Choy, Cecilia Li, Hubert Neman, Josh Wilczynski, Sharon Termini, John Hambrecht, Amanda C. Kowolik, Claudia M. |
| Description | Author Affiliation: Neman J ( Divisions of Neurosurgery and Pathology, Departments of Molecular Medicine, Immunology, and Neurobiochemistry, and Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010.); |
| Abstract | Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 3 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Brain Neoplasms Breast Neoplasms Pathology Gene Expression Regulation, Neoplastic Gamma-Aminobutyric Acid Metabolism 4-Aminobutyrate Transaminase Cell Adhesion Molecules, Neuronal Cell Line, Tumor Cell Proliferation Extracellular Matrix Proteins GABA Plasma Membrane Transport Proteins Glutamate Decarboxylase Interneurons Microscopy, Fluorescence Neoplasm Metastasis Nerve Tissue Proteins Neurons Parvalbumins Phenotype Receptors, GABA-A Serine Endopeptidases Tumor Microenvironment Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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