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In vitro ovarian cancer model based on three-dimensional agarose hydrogel.

ABSTRACT: To establish a typical tumor model of ovarian cancer which may be more representative and reliable than traditional monolayer culture and pellet, agarose was used as cell vehicle to engineering tumor. Selection of agarose is based on its successful application in tissue engineering with both amenable mechanical and biological properties. In this study, ovarian cancer cell line SKOV3 was encapsulated in agarose hydrogel with cell aggregates and two-dimensional culture as controls. In vitro cell proliferation was assessed by MTT and cell viability was examined at time points of 2, 4, and 6 days. The expression of tumor malignancy markers including matrix metalloproteinase 2, matrix metalloproteinase 9, hypoxia-inducible factor-1?, and vascular endothelial growth factor-A was assessed by real-time polymerase chain reaction. The results showed that cells proliferated more rapidly in three-dimensional agarose culture than controls. Furthermore, upregulation of matrix metalloproteinase 9 and matrix metalloproteinase 2 activity and increased expression of vascular endothelial growth factor-A and hypoxia-inducible factor-1? were shown in agarose-engineered tumors. All the evidences demonstrated that agarose may provide a more favorable environment for cancer cell growth, mimicking the in vivo environment for tumor generation. The novel in vitro tumor model may be useful for the further investigation of anticancer therapeutics.

SUBMITTER: Xu G

PROVIDER: S-EPMC3924902 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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In vitro ovarian cancer model based on three-dimensional agarose hydrogel.

Xu Guojie G Yin Fuqiang F Wu Huayu H Hu Xuefeng X Zheng Li L Zhao Jinming J

Journal of tissue engineering 20140116

To establish a typical tumor model of ovarian cancer which may be more representative and reliable than traditional monolayer culture and pellet, agarose was used as cell vehicle to engineering tumor. Selection of agarose is based on its successful application in tissue engineering with both amenable mechanical and biological properties. In this study, ovarian cancer cell line SKOV3 was encapsulated in agarose hydrogel with cell aggregates and two-dimensional culture as controls. In vitro cell p ...[more]

PMID: 24551446

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Project description:Defining the final size and geometry of engineered tissues through precise control of the scalar and vector components of tissue growth is a necessary benchmark for regenerative medicine, but it has proved to be a significant challenge for tissue engineers. The growth plate cartilage that promotes elongation of the long bones is a good model system for studying morphogenetic mechanisms because cartilage is composed of a single cell type, the chondrocyte; chondrocytes are readily maintained in culture; and growth trajectory is predominately in a single vector. In this cartilage, growth is generated via a differentiation program that is spatially and temporally regulated by an interconnected network composed of long- and short-range signaling mechanisms that together result in the formation of functionally distinct cellular zones. To facilitate investigation of the mechanisms underlying anisotropic growth, we developed an in vitro model of the growth plate cartilage by using neonatal mouse growth plate chondrocytes encapsulated in alginate hydrogel beads. In bead cultures, encapsulated chondrocytes showed high viability, cartilage matrix deposition, low levels of chondrocyte hypertrophy, and a progressive increase in cell proliferation over 7 days in culture. Exogenous factors were used to test functionality of the parathyroid-related protein-Indian hedgehog (PTHrP-IHH) signaling interaction, which is a crucial feedback loop for regulation of growth. Consistent with in vivo observations, exogenous PTHrP stimulated cell proliferation and inhibited hypertrophy, whereas IHH signaling stimulated chondrocyte hypertrophy. Importantly, the treatment of alginate bead cultures with IHH or thyroxine resulted in formation of a discrete domain of hypertrophic cells that mimics tissue architecture of native growth plate cartilage. Together, these studies are the first demonstration of a tunable in vitro system to model the signaling network interactions that are required to induce zonal architecture in growth plate chondrocytes, which could also potentially be used to grow cartilage cultures of specific geometries to meet personalized patient needs.

Dataset Information

In vitro ovarian cancer model based on three-dimensional agarose hydrogel.

Publications

In vitro ovarian cancer model based on three-dimensional agarose hydrogel.

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