Neoplastic extracellular matrix environment promotes cancer invasion in vitro

Sundquist, Elias; Renko, Outi; Salo, Sirpa; Magga, Johanna; Cervigne, Nilva K.; Nyberg, Pia; Risteli, Juha; Sormunen, Raija; Vuolteenaho, Olli; Zandonadi, Flávia S.; Leme, Adriana Franco Paes; Coletta, Ricardo D.; Ruskoaho, Heikki; Salo, Tuula

doi:10.1016/j.yexcr.2016.04.003

Cited by 12 publications

(22 citation statements)

References 32 publications

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“…However, such protein mixtures lack the complex 3D architecture which also influences proteolytic actions during cell invasion [3]. The described organotypic leiomyoma 3D solid disc model utilizes human tissue material with authentic components of the tumour microenvironment (TME) such as fibroblasts, insoluble and soluble ECM components, and a complex tumour tissue architecture including nerves and vessels [3,4,5]. Although cells in the myoma discs are not viable, their presence is important as they simulate the in vivo tumour cellular environment [6].…”

Section: Extracellular Matrix (Ecm) Protein Mixtures Of Non-human Orimentioning

confidence: 99%

Human Tumor Tissue-Based 3D In Vitro Invasion Assays

Åström

Heljasvaara

Nyberg

et al. 2018

Methods in Molecular Biology

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Here we describe a protocol to utilize human benign leiomyoma tissue in in vitro 3D model that enables an assessment of cell invasion. The chapter also describes detailed instructions for image analysis to quantify the results. Leiomyoma is a benign tumor of the uterus which mimics authentic components of the tumor microenvironment including fibroblasts, vessels, collagen fibers, and extracellular protein composition. The leiomyoma invasion model represents a superior 3D model for cell invasion studies compared to the other non-human organotypic models.

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Section: Extracellular Matrix (Ecm) Protein Mixtures Of Non-human Orimentioning

confidence: 99%

Human Tumor Tissue-Based 3D In Vitro Invasion Assays

Åström

Heljasvaara

Nyberg

et al. 2018

Methods in Molecular Biology

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“…The hypoxic myoma discs mimic the TME of solid human tumours, and they contain a variety of non-vital cells and soluble invasion-related factors such as lysyl oxidase [16]. Recently, we showed that the invasion efficiency of the OTSCC cells into myoma depends on the amount of tenascin-C and soluble growth factors and their receptors in the tissue discs [17]. Myogel, on the other hand, provides a soluble human TME matrix for cancer studies.…”

Section: Introductionmentioning

confidence: 99%

Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro

Väyrynen

Piippo

Jämsä

et al. 2018

Experimental Cell Research

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Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and - 9 production. Finally, we analysed the long-term effects of IR by studying clones of previously irradiated and invaded HSC-3 cells. We found that in both human uterine leiomyoma-based extracellular matrix models IR inhibited the invasion of HSC-3 cells, but blocking HPSE1 activity combined with IR induced their invasion. Low doses of IR increased MMP expression and initiated epithelial-mesenchymal transition in cells cultured on myoma discs. We conclude that myoma models offer consistent methods for testing human carcinoma cell invasion and phenotypic changes during chemoradiation treatment. In addition, we showed that IR had long-term effects on MMP-2 and - 9, which might elicit different HSC-3 invasion responses when cells were under the challenge of HPSE1 inhibitors and IR.

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“…ECM remodelling is generally thought to promote invasive tumour phenotypes, including oral tongue cancer [ 53 – 55 ]. Secreted tumour EVs coated with fibronectin promote nascent adhesion assembly and increase cell motility [ 56 ].…”

Section: Introductionmentioning

confidence: 99%

Organotypic three-dimensional assays based on human leiomyoma–derived matrices

Salo

Dourado

Sundquist

et al. 2017

Phil. Trans. R. Soc. B

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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 in vitro. 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 in vitro 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 in vitro cancer assays.This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

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Neoplastic extracellular matrix environment promotes cancer invasion in vitro

Cited by 12 publications

References 32 publications

Human Tumor Tissue-Based 3D In Vitro Invasion Assays

Human Tumor Tissue-Based 3D In Vitro Invasion Assays

Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro

Organotypic three-dimensional assays based on human leiomyoma–derived matrices

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