Migration of recombinant IL-2-activated T and natural killer cells in the intercellular space of human H-2 glioma spheroids in vitro. A study on adhesion molecules involved.
The migration of rIL-2-activated T and NK cells into the intercellular space of glioma tissue was studied using multicellular spheroids grown from the human H-2 glioblastoma cell line as targets. Lymphocytes of all analyzed subtypes migrated into the spheroids, but CD56+ cells were particularly migratory. Lymphocytes and the H-2 tissue expressed adhesion molecule subunits for the following potential cell-cell or cell-matrix interactions: alpha 3 beta 1 (VLA-3) to fibronectin, laminin, and collagen; alpha 4 beta 1 (VLA-4) and alpha 5 beta 1 (VLA-5) to fibronectin; alpha 6 beta 1 (VLA-6) to laminin; alpha 4 beta 1 to VCAM-1; alpha L beta 2 (Leu-CAMa/LFA-1) to CD54 (ICAM-1); CD44 to fibronectin, collagen, laminin, hyaluronate; CD2 to CD58 (LFA-3); and CD56 (N-CAM) to CD56. In the H-2 tissue, CD54 and VCAM-1 were expressed as a gradient. The expression of CD54 was weak in the peripheral zone and the expression was stronger in the quiescent deeper zone, whereas the distribution of VCAM-1 showed an inversed pattern. The low expression of CD54 was up-regulated along the frontier of migrating lymphocytes. The migration was almost totally prevented by the anti-CD18 (beta 2) mAb IB4 and TS1/18, and also strongly inhibited by the anti-CD54 mAb LB-2. Instead, mAb known to inhibit the binding of beta 1 integrins to fibronectin were not significantly inhibitory. However, a combination of the GPEILDVPST and GRGDS peptides, which compete for the binding of alpha 4 beta 1 and alpha 5 beta 1 to fibronectin and may also affect other adhesion systems, partially prevented migration.
Department of Neurosurgery, University of Helsinki, Finland.
J
J
Jääskeläinen
A
A
Mäenpää
M
M
Patarroyo
C G
CG
Gahmberg
K
K
Somersalo
J
J
Tarkkanen
M
M
Kallio
T
T
Timonen
D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1; D007365:Intercellular Junctions / Q000648:ultrastructure; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology*; D007694:Killer Cells, Natural / Q000166:cytology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009940:Organoids; D016029:Receptors, Very Late Antigen / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D016023:Integrins; D007376:Interleukin-2; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1