Transcriptional Factor Repertoire of Breast Cancer in 3D Cell Culture Models

Abstract

Intratumor heterogeneity of breast cancer is driven by extrinsic factors from the tumor microenvironment (TME) as well as tumor cell–intrinsic parameters including genetic, epigenetic, and transcriptomic traits. The extracellular matrix (ECM), a major structural component of the TME, impacts every stage of tumorigenesis by providing necessary biochemical and biomechanical cues that are major regulators of cell shape/architecture, stiffness, cell proliferation, survival, invasion, and migration. Moreover, ECM and tissue architecture have a profound impact on chromatin structure, thereby altering gene expression. Considering the significant contribution of ECM to cellular behavior, a large body of work underlined that traditional two-dimensional (2D) cultures depriving cell–cell and cell–ECM interactions as well as spatial cellular distribution and organization of solid tumors fail to recapitulate in vivo properties of tumor cells residing in the complex TME. Thus, three-dimensional (3D) culture models are increasingly employed in cancer research, as these culture systems better mimic the physiological microenvironment and shape the cellular responses according to the microenvironmental cues that will regulate critical cell functions such as cell shape/architecture, survival, proliferation, differentiation, and drug response as well as gene expression. Therefore, 3D cell culture models that better resemble the patient transcriptome are critical in defining physiologically relevant transcriptional changes. This review will present the transcriptional factor (TF) repertoire of breast cancer in 3D culture models in the context of mammary tissue architecture, epithelial-to-mesenchymal transition and metastasis, cell death mechanisms, cancer therapy resistance and differential drug response, and stemness and will discuss the impact of culture dimensionality on breast cancer research.

Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype

“…This may be explained by the differences between the materials, where the collagen more closely resembles the natural basal lamina, which maintains the integrity and the polarity of epithelial cells. This particular cell architecture formed on 3D models affects their intracellular signaling pathways including those involved in proliferation. − …”

Identification of Genes Associated with the Impairment of Olfactory and Gustatory Functions in COVID-19 via Machine-Learning Methods

“…NUDT5 ( ENSG00000165609.13 ) was predicted by LightGBM and LASSO. It is reported to participate in the viral infection associated with signal transmission [ 44 , 45 ]. As for its specific role in association with COVID-19 compliments, the low expression level of the gene has been observed in severely infected cells [ 46 ].…”

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

“…These studies have been started in some research groups in parallel with organoid cultures, who are developing the isolation of cells and the optimisation of bioinks, developing protocols to print and culture patient-derived 3D structures, and comparing in vitro and in vivo drug sensitivity with therapeutic treatment results [78][79][80]. These models also have advantages and disadvantages, and in addition, there are several summaries and reviews about these subjects [21]. Our further aim is to investigate 3D bioprinted breast, glioma and ovarian TMS specimens as novel approaches for investigating drug responses in our next studies, with clinical collaboration (after obtaining ethical approval).…”

“…The comparison of the recently developed 3D culturing technology and with 2D cell cultures and their drug sensitivity test results has shown that 3D models can more reliably show the in vivo characteristics of cancer cells. The reduced drug sensitivity of 3D cell cultures (mainly the same in vivo) [19] with reduced proliferation [20], altered gene expressions [21], morphology [22], and invasion [23] were described in many study models and tumour cell types dependently. Based on these findings, these systems can be suggested for the promotion of pharmaceutical developments and the testing of new drug candidates.…”