3D Culture Modeling of Metastatic Breast Cancer Cells in Additive Manufactured Scaffolds

Citations Over TimeTop 18% of 2022 papers

Abstract

Cancer biology research is increasingly moving toward innovative in vitro 3D culture models, as conventional and current 2D cell cultures fail to resemble in vivo cancer biology. In the current study, porous 3D scaffolds, designed with two different porosities along with 2D tissue culture polystyrene (TCP) plates were used with a model breast cancer human cell line. The 3D engineered system was evaluated for the optimal seeding method (dynamic versus static), adhesion, and proliferation rate of MDA-MB-231 breast cancer cells. The expression profiles of proliferation-, stemness-, and dormancy-associated cancer markers, namely, ki67, lamin A/C, SOX2, Oct3/4, stanniocalcin 1 (STC1), and stanniocalcin 2 (STC2), were evaluated in the 3D cultured cells and compared to the respective profiles of the cells cultured in the conventional 2D TCP. Our data suggested that static seeding was the optimal seeding method with porosity-dependent efficiency. Moreover, cells cultured in 3D scaffolds displayed a more dormant phenotype in comparison to 2D, which was manifested by the lower proliferation rate, reduced ki67 expression, increased lamin A/C expression, and overexpression of STCs. The possible relationship between the cell affinity to different extracellular matrix (ECM) proteins and the RANK expression levels was also addressed after deriving collagen type I (COL-I) and fibronectin (FN) MDA-MB-231 filial cell lines with enhanced capacity to attach to the respective ECM proteins. The new derivatives exhibited a more mesenchymal like phenotype and higher RANK levels in relation to the parental cells, suggesting a relationship between ECM cell affinity and RANK expression. Therefore, the present 3D cell culture model shows that cancer cells on printed scaffolds can work as better representatives in cancer biology and drug screening related studies.

Related Papers

• → A fibronectin self-assembly site involved in fibronectin matrix assembly: reconstruction in a synthetic peptide.(1992)166 cited
• → Monoclonal antibody to fibronectin which inhibits extracellular matrix assembly(1987)37 cited
• → Studies of extracellular fibronectin matrix formation with fluoresceinated fibronectin and fibronectin fragments(1985)25 cited
• Plasma fibronectin contributes to fibronectin in tissues.(1985)
• → Concurrent modulation of cell surface fibronectin and adhesion to fibronectin in hepatoma cells(1983)7 cited