ASSESSMENT OF LAMININ-MEDIATED GLIOMA INVASION IN-VITRO AND BY GLIOMATUMORS ENGRAFTED WITHIN RAT SPINAL-CORD

Cell motility within central nervous system (CNS) neuropil may be larg ely restricted yet infiltration by glioma cells is commonly observed. Glioma cells remodel nervous tissue and may assemble extracellular mat rix in order to migrate. We examined the rat C6 glioma cell line for l aminin expression and response in vitro and following engraftment into rat spinal cord. C6 cell cultures expressed laminin-2. C6 cells attac hed equally well to substrates of purified laminin-1 and laminin-2 and laminin-2-enriched C6 conditioned medium. In contrast, C6 cell migrat ion was substantially greater on laminin-2 and C6-derived substrata th an on laminin-1. Glioma cell attachment to laminin-1 and -2 was largel y 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 syntheti c basement membrane. Anti-beta(1) integrin antibody selectively inhibi ted cell migration and invasion on laminin-2 substrata without affecti ng percent cell attachment. These findings suggest C6 cell migration a nd invasion are promoted by autocrine release of laminin-2 and involve LPB110 and beta(1) integrin laminin receptors. A possible role for la minin-2 in CNS infiltration in vivo was examined following glioma engr aftment into rat spinal cord. Engrafted C6 tumors share many histologi c features of invasive human glioma. Engrafted glioma cells expressed laminin, LBP110 and beta(1) integrin antigens, indicating the molecula r mechanisms of C6 motility observed in culture may contribute to glio ma invasion in vivo. NMR and corroborative immunocytochemistry provide d precise means to monitor tumor progression following glioma engraftm ent into rat spinal cord. Advantages of this glioma model are discusse d regarding the assessment of anti-adhesive therapies in vivo.