Assessment of laminin-mediated glioma invasion in vitro and by glioma tumors engrafted within rat spinal cord |
| |
Authors: | David Muir Jennifer Johnson Mumtaz Rojiani Ben A. Inglis Amyn Rojiani Bernard L. Maria |
| |
Affiliation: | (1) The Developmental Neuro-Oncology Laboratory, Division of Neurology, Department of Pediatrics, University of Florida College of Medicine, 32610 Gainesville, FL, USA;(2) Department of Neuroscience, University of Florida College of Medicine, 32610 Gainesville, FL, USA;(3) Center for Structural Biology, Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, 32610 Gainesville, FL, USA;(4) Neuropathology Section, Department Pathology and Laboratory Medicine, University of Florida College of Medicine, 32610 Gainesville, FL, USA |
| |
Abstract: | Summary Cell motility within central nervous system (CNS) neuropil may be largely restricted yet infiltration by glioma cells is commonly observed. Glioma cells remodel nervous tissue and may assemble extracellular matrix in order to migrate. We examined the rat C6 glioma cell line for laminin expression and response in vitro and following engraftment into rat spinal cord. C6 cell cultures expressed laminin-2. C6 cells attached equally well to substrates of purified laminin-1 and laminin-2 and laminin-2-enriched C6 conditioned medium. In contrast, C6 cell migration was substantially greater on laminin-2 and C6-derived substrata than on laminin-1. Glioma cell attachment to laminin-1 and -2 was largely inhibited by antibody to the laminin receptor LBP110 and by an IKVAV peptide but not by YIGSR or control peptides. IKVAV peptide and anti-LBP110 antibodies also inhibited glioma cell invasion through synthetic basement membrane. Anti- 1 integrin antibody selectively inhibited cell migration and invasion on laminin-2 substrata without affecting percent cell attachment. These findings suggest C6 cell migration and invasion are promoted by autocrine release of laminin-2 and involve LPB110 and 1 integrin laminin receptors.A possible role for laminin-2 in CNS infiltration in vivo was examined following glioma engraftment into rat spinal cord. Engrafted C6 tumors share many histologic features of invasive human glioma. Engrafted glioma cells expressed laminin, LBP110 and 1 integrin antigens, indicating the molecular mechanisms of C6 motility observed in culture may contribute to glioma invasion in vivo. NMR and corroborative immunocytochemistry provided precise means to monitor tumor progression following glioma engraftment into rat spinal cord. Advantages of this glioma model are discussed regarding the assessment of anti-adhesive therapies in vivo. |
| |
Keywords: | C6 glioma spinal cord migration invasion laminin peptide antagonist NMR |
本文献已被 SpringerLink 等数据库收录! |
|