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.