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

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.

Bibliometric Analysis of Global Research on Tumor Dormancy

“…These models [37] have achieved significant breakthroughs in mimicking the tumor microenvironment, understanding the regulation of tumor dormancy by the tumor microenvironment, and exploring the interactions between tumor cells and the microenvironment [38]. In addition, when immunotherapy is of great interest [39], co-culture systems containing other cells, such as immune cells designed using 3D models, may help us improve our success rate regarding drug screening and validation [40]. Therefore, in the future, research will still focus on several cancer tissues, as mentioned above, and studies on tumor dormant tumor microenvironments will remain prevalent [41].…”

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

“…STC1 was found to be a biomarker in many diseases [52][53][54][55] . In this study, we found that STC1 was highly expressed in HCC and was closely correlated with poor prognosis in HCC patients.…”

Research Progress in the Field of Tumor Model Construction Using Bioprinting: A Review

“…This scaffold not only promotes cell growth but also provides essential cues from the natural biophysics and biochemical environment, which are crucial for regulating tumor cell functions. 84 Currently, scaffolds for in vitro cancer modeling have evolved from natural hydrogels (such as proteins, polysaccharides), synthetic hydrogels (such as polyethylene glycol, peptides), and hybrid materials (with high water content, tissue-like bioresponsiveness, viscoelasticity, and mechanical properties). Advances in microfabrication techniques in recent years have enabled more complex and precise hydrogel platforms, which can replicate the fundamental characteristics of the tumor microenvironment (TME).…”