Bug, G. and Rossmanith, T. and Henschler, R. and Kunz-Schughart, L. A. and Schroeder, B. and Kampfmann, M. and Kreutz, M. and Hoelzer, D. and Ottmann, O. G. (2002) Rho family small GTPases control migration of hematopoietic progenitor cells into multicellular spheroids of bone marrow stroma cells. JOURNAL OF LEUKOCYTE BIOLOGY, 72 (4). pp. 837-845. ISSN 0741-5400
Full text not available from this repository. (Request a copy)Abstract
Seeding of hematopoietic progenitor cells (HPC) into the bone marrow requires a complex interaction between cell membrane and adhesion systems and cell signaling pathways. We established a multicellular, spheroid coculture model to study HPC migration in a three-dimensional stromal environment. Here, entry of primary CD34(+) cells into stroma cell spheroids was independent of the integrins very late antigen (VLA)-4, VLA-5, lymphocyte function-associated antigen-1, and the chemokine receptor CXCR4. Experiments using a panel of bacterial toxins selectively targeting key regulators of cellular locomotion, the Rho family small GTPases Rho, Rac, and Cdc42, revealed a considerable reduction or even abrogation of TF-1 cell migration without an increase of apoptosis or impairment of proliferation. Pertussis toxin, an inhibitor of Galpha(i) proteins, showed a similar effect. In some in vitro invasion assays, phosphatidylinositol-3 kinase (PI-3K) was shown to mediate Rac- and Cdc42-induced cell motility and invasion. However, inhibition of the PI-3K pathway by LY294002 did not impair TF-1 cell migration in our three-dimensional model system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SORDELLII LETHAL TOXIN; T-LYMPHOCYTES; SIGNAL-TRANSDUCTION; ADHESION MOLECULES; TUMOR SPHEROIDS; STEEL FACTOR; PROTEINS; DIFFERENTIATION; MOBILIZATION; POLARIZATION; very late antigen; lymphocyte function-associated antigen-1; phosphatidylinositol-3 kinase; pertussis toxin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Oct 2021 05:42 |
| Last Modified: | 05 Oct 2021 05:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39837 |
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