Sehgal A, Ricks S, Warrick J, Boynton A L, Murphy G P
Department of Neurological Surgery, University of California at San Francisco 94103, USA.
Anticancer Res. 1999 Nov-Dec;19(6B):4947-53.
Human Nr-CAM (Neuroglia related Cell Adhesion Molecule) is over expressed in glioblastoma multiforme tissue (GMT) as compared to normal brain tissue (NBT).
We transfected a human glioblastoma cell line (2020-CRL) with a vector that overexpresses antisense hNr-CAM using a CMVpromoter.
Antisense hNr- CAM caused reduction in the native hNr-CAM expression, changed cell morphology, reduced the cell proliferation rate and lengthening of the cell cycle. Furthermore, antisense hNr-CAM overexpression in these cells caused extensive reduction in the number of soft agar colonies and invasion through extra cellular matrix (ECM) gel in vitro. Subcutaneous injection of antisense hNr-CAM overexpressing glioblastoma cells into nude mice caused complete inhibition of tumor formation as compared to vector only transfected cells. Intra-tumoral inoculation of antisense hNr-CAM expressing plasmid also caused slow tumor growth in nude mice in vivo.
On the basis of these results, we conclude that hNr-CAM is a valid target for potential gene therapy of glioblastoma tumors.