CD44s-targeted treatment with monoclonal antibody blocks intracerebral invasion and growth of 9L gliosarcoma.
Glioma invasiveness is a complex process involving recognition and attachment of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. CD44 is a group of transmembrane adhesion molecules found on a wide variety of cells including gliomas that has been suggested as the principal mediator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo. High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95%+/-2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5%+/-0.4%)--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--as compared to untreated (16.1%+/-2.2%) or sham-treated rats (16%+/-3.7% to 16.1%+/-3%). We conclude that CD44s-targeted treatment with specific mAb may be an effective means for preventing glioma progression.
Gunia
S
S
Institute of Neuropathology, Hannover Medical School, Germany.
Hussein
S
S
Radu
D L
DL
Pütz
K M
KM
Breyer
R
R
Hecker
H
H
Samii
M
M
Walter
G F
GF
Stan
A C
AC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology; D018960:Hyaluronan Receptors / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D051381:Rats; D011923:Rats, Nude; D018675:Toxicity Tests; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors