TY - JOUR
T1 - Enhanced chemoresistance of squamous carcinoma cells grown in 3D cryogenic electrospun scaffolds
AU - Bulysheva, Anna A.
AU - Bowlin, Gary L.
AU - Petrova, Stella P.
AU - Yeudall, W. Andrew
PY - 2013/10
Y1 - 2013/10
N2 - It is critically important to study head and neck squamous cell carcinoma tumorigenic mechanisms in order to gain a better understanding of tumor development, progression, and treatment. Unfortunately, a representative three-dimensional (3D) model for these evaluations has yet to be developed. The purpose of this study was to replicate tumor extracellular matrix (ECM) morphology utilizing electrospinning technology. First, the tumor ECM was evaluated by decellularizing tumor samples and analyzing the fibrous structure of the ECM by scanning electron microscopy. Cryogenic electrospun silk scaffolds were then fabricated to mimic the tumor ECM, and were found to be similar in fiber orientation and fiber dimensions to the native tumor ECM. Tumor cells were cultured on these ECM mimicking scaffolds and compared to an in vivo model of the same derivative human tumor in terms of proliferation and differentiation. The tumor cells in the 3D model show similar phenotypes to those found in vivo, contrasting to the same cells grown in two-dimensional (2D) culture. The sensitivity of the tumor cells to paclitaxel was compared between 2D culture and 3D culture. The results indicate that increased drug concentrations, orders of magnitude higher than the IC90 for 2D culture, had minimal effects on HN12 cell viability in the 3D model. In conclusion, an in vitro tumor model has been developed that will allow for a better understanding of tumor biology and aid chemotherapeutic drug development and accurate evaluation of drug efficacy.
AB - It is critically important to study head and neck squamous cell carcinoma tumorigenic mechanisms in order to gain a better understanding of tumor development, progression, and treatment. Unfortunately, a representative three-dimensional (3D) model for these evaluations has yet to be developed. The purpose of this study was to replicate tumor extracellular matrix (ECM) morphology utilizing electrospinning technology. First, the tumor ECM was evaluated by decellularizing tumor samples and analyzing the fibrous structure of the ECM by scanning electron microscopy. Cryogenic electrospun silk scaffolds were then fabricated to mimic the tumor ECM, and were found to be similar in fiber orientation and fiber dimensions to the native tumor ECM. Tumor cells were cultured on these ECM mimicking scaffolds and compared to an in vivo model of the same derivative human tumor in terms of proliferation and differentiation. The tumor cells in the 3D model show similar phenotypes to those found in vivo, contrasting to the same cells grown in two-dimensional (2D) culture. The sensitivity of the tumor cells to paclitaxel was compared between 2D culture and 3D culture. The results indicate that increased drug concentrations, orders of magnitude higher than the IC90 for 2D culture, had minimal effects on HN12 cell viability in the 3D model. In conclusion, an in vitro tumor model has been developed that will allow for a better understanding of tumor biology and aid chemotherapeutic drug development and accurate evaluation of drug efficacy.
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U2 - 10.1088/1748-6041/8/5/055009
DO - 10.1088/1748-6041/8/5/055009
M3 - Article
C2 - 24057893
AN - SCOPUS:84885361354
SN - 1748-6041
VL - 8
JO - Biomedical Materials (Bristol)
JF - Biomedical Materials (Bristol)
IS - 5
M1 - 055009
ER -