Abstract
Goal: 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. Methods: 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. Results: 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. Conclusions: 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.
Highlights
T HE cancer microenvironment is a complex system consisting of extracellular matrix, stromal cells, adipocytes, fluids and vasculature [1]
This system is dynamically remodeled during tumorigenesis leading to a constantly evolving temporal and spatial 3D structures with distinct physical and pathophysiological alterations conducive to tumors [2]
The cells grow in monolayers, lose polarity, and have an altered shape leading to changes in gene expression and splicing [3]–[7]
Summary
T HE cancer microenvironment is a complex system consisting of extracellular matrix, stromal cells, adipocytes, fluids and vasculature [1]. The cells grow in monolayers, lose polarity, and have an altered shape leading to changes in gene expression and splicing [3]–[7] It fails to recreate the complex 3D intercellular signaling cascades and cell-matrix interactions, hypoxic conditions characteristic of tumor microenvironment, and communication between cells in different niches [8]–[10]. The scaffolds provide a stable 3D environment for the cells to adhere, migrate, proliferate and differentiate [12] They closely mimic the microenvironment with hypoxia-like conditions and cellular niches. The synthetic material systems provide key information regarding cell migration and signaling cascades, but fail to consider the durotaxic and topotaxicmechanical properties and topographical cues, including roughness, curvature, porosity and fibrosity of the tumor microenvironment [18]–[22]
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