fully-human-tumor-based-matrix-three-dimensional-spheroid-invasion

Fully Human Tumor-based Matrix in Three-dimensional Spheroid Invasion Assay

Two-dimensional cell culture-based assays are commonly used in in vitro cancer research. However, they lack several basic elements that form the tumor ...

University of Helsinki

Finnish head and neck cancer (HNC) patients show signs of severe malnutrition already at presentation, measured by bioelectric impedance analysis (BIA). BIA may be a practical method to detect malnutrition, analyze body composition, and to identify high-risk patients in this population.

Bioelectrical impedance analysis of head and neck cancer patients at presentation.

The crosstalk between immune cells, cancer cells, and extracellular vesicles (EVs) secreted by cancer cells remains poorly understood. We created three-dimensional (3D) cell culture models using human leiomyoma discs and Myogel to study the effects of immune cells on highly (HSC-3) and less (SCC-25) invasive oral tongue squamous cell carcinoma (OTSCC) cell lines. Additionally, we studied the effects of EVs isolated from these cell lines on the cytotoxicity of CD8 T and NK cells isolated from three healthy donors. Our analysis included the effects of these EVs on innate immunity in zebrafish larvae. Activated immune cells significantly decreased the proliferation of both OTSCC cell lines and associated with a diminished invasion area of HSC-3 cells. In general, EVs from SCC-25 increased the cytotoxic activity of CD8 T and NK cells more than those from HSC-3 cells. However, this effect varied depending on the source and the immune and cancer cell subgroups. In zebrafish, the amount of IL-13 mRNA was decreased by SCC-25 EVs. This study describes promising  and  models to investigate interactions between immune cells, cancer cells, and EVs.

Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in  and  models.

Alongside cancer cells, tumours exhibit a complex stroma containing a repertoire of cells, matrix molecules and soluble factors that actively crosstalk between each other. Recognition of this multifaceted concept of the tumour microenvironment (TME) calls for authentic TME mimetics to study cancer  Traditionally, tumourigenesis has been investigated in non-human, three-dimensional rat type I collagen containing organotypic discs or by means of mouse sarcoma-derived gel, such as Matrigel However, the molecular compositions of these simplified assays do not properly simulate human TME. Here, we review the main properties and benefits of using human leiomyoma discs and their matrix Myogel for  assays. Myoma discs are practical for investigating the invasion of cancer cells, as are cocultures of cancer and stromal cells in a stiff, hypoxic TME mimetic. Myoma discs contain soluble factors and matrix molecules commonly present in neoplastic stroma. In Transwell, IncuCyte, spheroid and sandwich assays, cancer cells move faster and form larger colonies in Myogel than in Matrigel Additionally, Myogel can replace Matrigel in hanging-drop and tube-formation assays. Myogel also suits three-dimensional drug testing and extracellular vesicle interactions. To conclude, we describe the application of our myoma-derived matrices in 3D  cancer assays.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.

Article	Year
Bioelectrical impedance analysis of head and neck cancer patients at presentation. Acta oto-laryngologica\| PubMed ID: 28079435	2017
Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in and models. Oncotarget\| PubMed ID: 28947958	2017
Organotypic three-dimensional assays based on human leiomyoma-derived matrices. Philosophical transactions of the Royal Society of London. Series B, Biological sciences\| PubMed ID: 29158312	2018

Katja Tuomainen

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