Engineered Three-Dimensional Scaffolds Modulating Fate of Breast Cancer Cells Using Stiffness and Morphology Related Cell Adhesion

Abstract

Artificially engineering the tumor microenvironment in vitro as a vital tool for understanding the mechanism of tumor progression. In this study, we developed three-dimensional cell scaffold systems with different topographical features and mechanical properties but similar surface chemistry. The cell behavior was modulated by the topography and mechanical properties of the scaffold. Adenocarcinoma (MCF7), triple-negative (MDA-MB-231) and premalignant (MCF10AneoT) breast cancer cells were seeded on the scaffold systems. The cell viability, cell-cell interaction and cell-matrix interactions were analyzed. The preferential growth and alignment of specific population of cells were demonstrated. Among the different scaffolds, triple-negative breast cancer cells preferred honeycomb scaffolds while adenocarcinoma cells favored mesh scaffolds and premalignant cells preferred the aligned scaffolds. The 3D model system developed here can be used to support growth of only specific cell populations or for the growth of tumors. This model can be used for understanding the topographical and mechanical features affecting tumorigenesis, cancer cell growth and migration behavior of malignant and metastatic cancer cells.

PAMR1 is a favorable diagnostic and prognostic biomarker in hepatocellular carcinoma

“…The results of GO analysis then indicated that PAMR1-related genes were mainly enriched in the regulation of extracellular matrix organization, cell adhesion, and blood vessel development. These functions are closely associated with cancer; loss of cellular adhesion is a crucial step in tumor metastasis, whereas blood vessel development contributes to both tumor growth and spread 16,17 .…”

Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone–Tumor Niche

“…The authors determined that the geometry of PO250+ (fine checkerboard), with a pore size of 250 μm, was optimal towards eliciting strong cell proliferation and viability, as well as causing the expression of the liver-specific mRNA CYP3A4 and protein albumin [ 223 ]. With specific reference to the cellular behavior of cancer cells, Hanumantharao et al carried out an interesting study examining how different topographical features and mechanical properties of PCL scaffolds influenced human ER+ and triple negative breast cancer cells [ 227 ]. The authors found that human MCF-7 ER+ breast cancer cells proliferated well on a variety of different scaffold topographies, where the MCF-7 cells had a higher rate of proliferation on scaffolds with low Young’s modulus and stiffness.…”

“…The authors found that human MCF-7 ER+ breast cancer cells proliferated well on a variety of different scaffold topographies, where the MCF-7 cells had a higher rate of proliferation on scaffolds with low Young’s modulus and stiffness. On the other hand, human MDA-MB-231 triple negative breast cancer cells preferred scaffolds that had a high matrix stiffness [ 227 ]. These results suggest that cancer cells respond to changes in scaffold stiffness, mechanical properties, and topography, which should be considered when developing a 3D bioprinted scaffold to model the tumor microenvironment.…”

Embracing Mechanobiology in Next Generation Organ-On-A-Chip Models of Bone Metastasis

“…Different types of BCCs respond differently to various levels of matrix stiffness. Triple-negative BCCs favor honeycomb geometries with greater stiffness, adenocarcinoma MCF-7 cells prefer mesh scaffolds with low elastic modulus, and pre-malignant cells favor aligned scaffolds with high stiffness and contact guidance ( 22 ). Additionally, it has been reported that rigidity sensing by healthy mammary cells is impaired in BCCs but remains active in normal mammary cells ( 23 ).…”