title: Bradykinin enhances invasion of malignant glioma into the brain parenchyma by inducing cells to undergo amoeboid migration.
abstract: The molecular and cellular mechanisms governing cell motility and directed migration in response to the neuropeptide bradykinin are largely unknown. Here, we demonstrate that human glioma cells whose migration is guided by bradykinin generate bleb-like protrusions. We found that activation of the B2 receptor leads to a rise in free Ca(2+) from internal stores that activates actomyosin contraction and subsequent cytoplasmic flow into protrusions forming membrane blebs. Furthermore Ca(2+) activates Ca(2+)-dependent K(+) and Cl(-) channels, which participate in bleb regulation. Treatment of gliomas with bradykinin in situ increased glioma growth by increasing the speed of cell migration at the periphery of the tumour mass. To test if bleb formation is related to bradykinin-promoted glioma invasion we blocked glioma migration with blebbistatin, a blocker of myosin kinase II, which is necessary for proper bleb retraction. Our findings suggest a pivotal role of bradykinin during glioma invasion by stimulating amoeboid migration of glioma cells.
authors.affiliation: Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Seifert
authors.affiliation: Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA sontheimer@uab.edu.
authors.forename: Harald
authors.initials: H
authors.lastname: Sontheimer
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D015221:Potassium Channels; D015222:Sodium Channels; C472645:blebbistatin; D001920:Bradykinin; D002118:Calcium