Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D.
The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. The roles of HA cell surface receptors and hyaluronidases (HAses) in this process are still controversial. In order to investigate their involvement in cancer pathogenesis, we developed a reticulated HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied thirteen cell lines, from primary tumors or metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. The number of colonies, which reflects tumor cell invasiveness, ranged from 7 to 193 after 5 days of culture. Invasion was dependent on the production of HAse as well as other factors. Optimal colonization occurred when cells released HAse, lacked HA-binding sites and did not secrete HA. Moreover, we describe for the first time a HAse activity at physiological pH that may be responding to the confinement of the enzyme in a three-dimensional structure. We show here that this reticulated matrix provides a three-dimensional model for investigating mechanisms involved in malignant invasion.
Groupe de Recherche sur le Micro-Environnement et le Renouvellement Cellulaire Intégré (M.E.R.C.I., UPRES EA 2122), Faculté de Médecine Pharmacie, Université de ROUEN, 22, boulevard Gambetta, 76183 Rouen, France. laurent.david@uni-rouen.fr
Laurent
L
David
Virginie
V
Dulong
Didier
D
Le Cerf
Claude
C
Chauzy
Vic
V
Norris
Bertrand
B
Delpech
Marek
M
Lamacz
Jean-Pierre
JP
Vannier
D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D009439:Neuraminidase / Q000378:metabolism
D001672:Biocompatible Materials; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D006493:Heparin; D009439:Neuraminidase; D006821:Hyaluronoglucosaminidase