TY - JOUR
T1 - 3D Culture Modeling of Metastatic Breast Cancer Cells in Additive Manufactured Scaffolds
AU - Nanou, Afroditi
AU - Lorenzo-Moldero, Ivan
AU - Gazouleas, Kyriakos D.
AU - Cortese, Barbara
AU - Moroni, Lorenzo
N1 - Funding Information:
We are grateful to the European Community’s Seventh Framework Program (FP7/2007-2013) (grant agreement no. 305436, STELLAR). This research project was possible thanks to the support of the Dutch province of Limburg. The authors also gratefully thank the following agencies for their financial support: “Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia DGR n.2117 del 21/11/2018, CUP B84I18000540002; “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED)-FISR/MIUR-CNR delibera CIPE n.3449 del 7-08-2017, CUP B83B17000010001; AIRC under IG 2021 - ID. 26328 project-PI B.C.
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/6/22
Y1 - 2022/6/22
N2 - 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.
AB - 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.
KW - breast cancer
KW - scaffolds
KW - three-dimensional bioprinting
KW - tissue engineering
KW - tumor microenvironment
KW - UT-Hybrid-D
UR - http://www.scopus.com/inward/record.url?scp=85132455543&partnerID=8YFLogxK
U2 - 10.1021/acsami.2c07492
DO - 10.1021/acsami.2c07492
M3 - Article
C2 - 35687666
AN - SCOPUS:85132455543
SN - 1944-8244
VL - 14
SP - 28389
EP - 28402
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 24
ER -