title: Impact of stress and mast cells on brain metastases.
abstract: Metastases continue to be the chief cause of morbidity and mortality for many tumors, including brain metastases of lung and mammary adenocarcinoma. Stress appears to increase metastases, but the mechanism is not understood. Recent evidence suggests that local inflammation is conducive for cancer growth and a unique immune cell, the mast cell, accumulates in the stroma surrounding tumors and is critically located at the blood-brain-barrier (BBB). Mast cells express receptors for and can be stimulated by corticotropin-releasing hormone (CRH), secreted under stress, to release mediators such as histamine, IL-8, tryptase and vascular endothelial growth factor (VEGF), which disrupt the BBB permitting metastases. Stress and mast cells could serve as new targets for drug development to prevent brain metastases, especially since CRH receptor antagonists and brain mast cell inhibitors have recently been developed.
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA. theoharis.theoharides@tufts.edu
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
authors.forename: Jacek J
authors.initials: JJ
authors.lastname: Rozniecki
authors.forename: Gary
authors.initials: G
authors.lastname: Sahagian
authors.forename: Stanley
authors.initials: S
authors.lastname: Jocobson
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Kempuraj
authors.forename: Pio
authors.initials: P
authors.lastname: Conti
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kalogeromitros
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001932:Brain Neoplasms / Q000209:etiology* / Q000556:secondary*; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism*; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology
chemical_list: D018836:Inflammation Mediators