Engineering tumors with 3D scaffolds.
Microenvironmental conditions control tumorigenesis and biomimetic culture systems that allow for in vitro and in vivo tumor modeling may greatly aid studies of cancer cells' dependency on these conditions. We engineered three-dimensional (3D) human tumor models using carcinoma cells in polymeric scaffolds that recreated microenvironmental characteristics representative of tumors in vivo. Strikingly, the angiogenic characteristics of tumor cells were dramatically altered upon 3D culture within this system, and corresponded much more closely to tumors formed in vivo. Cells in this model were also less sensitive to chemotherapy and yielded tumors with enhanced malignant potential. We assessed the broad relevance of these findings with 3D culture of other tumor cell lines in this same model, comparison with standard 3D Matrigel culture and in vivo experiments. This new biomimetic model may provide a broadly applicable 3D culture system to study the effect of microenvironmental conditions on tumor malignancy in vitro and in vivo.
Fischbach
Claudia
C
School of Engineering and Applied Sciences, Harvard University, 40 Oxford Street; Cambridge, Massachusetts 02138, USA.
Chen
Ruth
R
Matsumoto
Takuya
T
Schmelzle
Tobias
T
Brugge
Joan S
JS
Polverini
Peter J
PJ
Mooney
David J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D009062:Mouth Neoplasms; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D023822:Tissue Engineering / Q000379:methods*
D000970:Antineoplastic Agents