title: Gangliosides regulate tumor cell adhesion to collagen.
abstract: The ability of tumor cells to adhere to extracellular matrix proteins is critical for migration and invasion. The factors that regulate tumor cell adhesion are poorly characterized. Gangliosides promote platelet adhesion and may also play a role in the adhesion of other cell types. We hypothesized that pharmacological depletion of membrane gangliosides from adherent cells would abrogate adhesion to collagen and promote migration and invasion. To test these hypotheses, LA-N1 neuroblastoma cells, which avidly adhere to collagen and are rich with membrane gangliosides (43.69 nmol/10(8) cells), were cultured in the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl. Endogenous gangliosides were reduced by 98% (0.76 nmol/10(8) cells) and adhesion to collagen decreased by 67%. There were no changes in cell morphology, viability, proliferation rate or apoptosis. Pre-incubation of ganglioside-depleted cells in conditioned medium from control cells restored adhesion to collagen (0.45 +/- 0.002), comparable to that of control cells (0.49 +/- 0.035). Similarly, pre-incubation of ganglioside-depleted cells with purified GD2 completely restored adhesion in a concentration-dependent manner. When LA-N1 cells were cultured with retinoic acid, a biological response modifier known to increase endogenous gangliosides, adhesion to collagen increased. Next, we questioned whether changes in adhesion would be reflected as changes in migration and invasion. Cells depleted of endogenous cellular gangliosides migrated more than control cells. Finally, control cells replete with their endogenous gangliosides demonstrated less invasive potential than control cells. The data demonstrate that endogenous tumor gangliosides increase neuroblastoma cell adhesion to collagen and reduce migration and invasion in vitro.
authors.affiliation: Department of Pediatrics, Rush Children's Hospital, Rush University, Chicago, Illinois 60612, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kazarian
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Jabbar
authors.forename: Fei-Qui
authors.initials: FQ
authors.lastname: Wen
authors.forename: Dharmesh A
authors.initials: DA
authors.lastname: Patel
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Valentino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005732:Gangliosides / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008858:Microscopy, Phase-Contrast; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D005732:Gangliosides; D009025:Morpholines; C033110:RV 538; D003094:Collagen