Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity.
The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. In order to investigate the sensitivity of cancer cells to antimitotic agents, we developed a cross-linked HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied three cell lines (SA87, NCI-H460 and H460M), from primary tumors and metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. Concurrently, we studied the growth of these cell lines in a usual monolayer culture system. In these two models, increasing concentrations of doxorubicin and 5-fluorouracil were evaluated for their ability to inhibit tumor cell growth and colony formation. Taken together, our data suggest that the cancer cells were more resistant in the three-dimensional model than in monolayer cell systems. The antimitotic drugs were efficient after 24h of treatment in the monolayer cultures, whereas they were significantly efficient only after one week of incubation in the HA hydrogels. Herein, we show that this cross-linked matrix provides a three-dimensional model particularly appropriate for investigating mechanisms involved in cancer cell line sensitivity to antimitotic drugs.
David
Laurent
L
Groupe de Recherche sur le Micro-Environnement et le Renouvellement Cellulaire Intégré (MERCI, UPRES EA 3829), Faculté de Médecine Pharmacie, Université de Rouen, 22 boulevard Gambetta, 76183 Rouen, France. laurent.david@etu.univ-rouen.fr
Dulong
Virginie
V
Le Cerf
Didier
D
Cazin
Lionel
L
Lamacz
Marek
M
Vannier
Jean-Pierre
JP
D000970:Antineoplastic Agents / Q000494:pharmacology; D001672:Biocompatible Materials; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid; D020100:Hydrogels; D008954:Models, Biological; D014410:Tumor Stem Cell Assay / Q000379:methods*
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D020100:Hydrogels; D004317:Doxorubicin; D006820:Hyaluronic Acid; D005472:Fluorouracil