Biomimetic 3D Clusters Using Human Adipose Derived Mesenchymal Stem Cells and Breast Cancer Cells: A Study on Migration and Invasion of Breast Cancer Cells

Abstract

Invasion and metastasis of cancer directly related to human death have been associated with interactions among many different types of cells and three-dimensional (3D) tissue matrices. Precise mechanisms related to cancer invasion and metastasis still remain unknown due to their complexities. Development of tumor microenvironment (TME)-mimicking system could play a key role in understanding cancer environments and in elucidating the relating phenomena and their driving forces. Here we report a facile and novel platform of 3D cancer cell-clusters using human adipose-derived mesenchymal stem cells (hASCs) and breast cancer cells (MDA-MB-231) within a collagen gel matrix to show cancer invasion in the cell and extracellular matrix (ECM). Both clusters A (hASC only) and AC (hASC and MDA-MB-231) exhibited different behaviors and expressions of migration and invasion, as observed by the relating markers such as fibronectin, α-SMA, and CXCR4. hASCs showed a protrusive migration from a cluster center, whereas MDA-MB-231 spread out radially followed by hASC migration. Finally, the effect of matrix was further discussed by varying collagen gel densities. The new biomimetic system of 3D cancer clusters developed here has the potential to be utilized for research on migration and invasion of cancer cells in extracellular matrices.

Multiparametric Analysis of Oncology Drug Screening with Aqueous Two-Phase Tumor Spheroids

“…4−6 To improve drug discovery outcomes, it is critical to employ cellular models that mimic structural, biological, and functional properties of tumors. 7 Spheroids are 3D compact clusters of cancer cells that model avascular solid tumors, close cell−cell contacts, matrix deposition and cell-matrix interactions, diffusion limitations of oxygen, nutrients, metabolites, and waste products, cell migration from solid tumors, 8 and gene expression profiles of original tumors. 9−15 Despite their clear benefits, spheroids are not routinely used in compound screening applications for anticancer drug discovery.…”

Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function

“…Epithelial cells themselves do not easily form stable constructs without neighboring stromal cells, which provide a matrix for cell adhesion and contract forces in vitro and in vivo; however, epithelial cells such as hepatocytes weakly form 3D constructs via cell-cell interactions mediated by membrane junction proteins, such as E-cadherin [48]. Previously, we reported that epithelial cancer cells and endothelial cells did not form 3D aggregates in PS-MBP-FGF2 [47]. Similarly, in this study, miHeps alone hardly formed spheroids in PS-MBP-FGF2, which could possibly explain their inability to adhere onto the MBP-FGF2-coated PS surface or the absence of aggregation-mediated spheroid-forming conditions, such as under agitation and centrifugation.…”

“…Previously, we developed 3D microtissue models for cell therapy and tissue regeneration using PS-MBP-FGF2, which promotes the spontaneous formation of self-organized spheroids [42,47]. Furthermore, to produce functional 3D hepatocytes with high reproducibility, rapidity (<24 h), and ease of handling, in this study, we utilized the PS-MBP-FGF2 matrix as an artificial matrix for the spontaneous formation of hASC-miHep co-spheroids.…”

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

“…228 The metastatic properties of tumor cells can be affected by MSCs by facilitating epithelial–mesenchymal transition (EMT) and increasing tumor cell mobility. 229…”