title: Phosphatidylinositol 3-kinase in the G protein-coupled receptor-induced chemokinesis and chemotaxis of MDA-MB-468 breast carcinoma cells: a comparison with leukocytes.
abstract: The polarization of tumor cells and leukocytes into a front end and a rear end is a crucial prerequisite for their autonomous, directed movement. Phosphatidylinositol 3-kinase (PI3K) is assumed to play an important role in this polarization process, whereas the results obtained with different cell types and different migration assays widely vary. Thus, we conducted a comparative study on the role of the PI3K in the locomotor activity and directionality of the migration of tumor cells on the example of MDA-MB-468 breast carcinoma cells in comparison with CTLs and neutrophil granulocytes. We used our well-established, collagen-based, three-dimensional migration assay for the investigation of the chemokinesis and chemotaxis of these cells. Our results show that the role of the PI3K in the regulation of migratory activity is distinct between the investigated cell types: the migration of CTLs and MDA-MB-468 cells was impaired by the inhibition of the PI3K with wortmannin, whereas neutrophil granulocytes were only slightly affected. However, neither cell type was impaired in the ability to respond chemotactically to gradients of ligands to G protein-coupled receptors. Thus, the PI3K contributes to the regulation of migratory activity but not to the directionality of migration of MDA-MB-468 breast carcinoma cells. As a further conclusion with regard to cancer treatment, the PI3K is not a suitable target for the inhibition of metastasis formation, because the migration of leukocytes is also affected, which leads to a dysfunction of the immune defense.
authors.affiliation: Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Bastian
authors.forename: Birte
authors.initials: B
authors.lastname: Posch
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lang
authors.forename: Bernd
authors.initials: B
authors.lastname: Niggemann
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Zaenker
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: Frank
authors.initials: F
authors.lastname: Entschladen
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology; D002633:Chemotaxis; D002634:Chemotaxis, Leukocyte; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000032:analysis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000032:analysis; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000166:cytology / Q000502:physiology*
chemical_list: D018129:Phosphatidylinositol Phosphates; D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human