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

Salo, Tuula; Dourado, Maurício Rocha; Sundquist, Elias; Apu, Ehsanul Hoque; Alahuhta, Ilkka; Tuomainen, Katja; Vasara, Jenni; Al‐Samadi, Ahmed

doi:10.1098/rstb.2016.0482

Cited by 34 publications

(38 citation statements)

References 89 publications

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“…Cancer cell invasion was assessed in the myoma organotypic cultures and performed according to the previously published myoma model protocol 17,18 . Briefly, uterine leiomyoma tissues were obtained from routine surgery after informed consent of the donors.…”

Section: Myoma Organotypic Invasion Modelmentioning

confidence: 99%

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Alburquerque-González

Bernabé-García

Montoro-García

et al. 2020

Exp Mol Med

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Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and is characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) and overexpression of fascin1, a key protein in actin bundling that plays a causative role in tumor invasion and is overexpressed in different cancer types with poor prognosis. In silico screening of 9591 compounds, including 2037 approved by the Food and Drug Administration (FDA), was performed, and selected compounds were analyzed for their fascin1 binding affinity by differential scanning fluorescence. The results were compared with migrastatin as a typical fascin1 inhibitor. In silico screening and differential scanning fluorescence yielded the FDA-approved antidepressant imipramine as the most evident potential fascin1 blocker. Biophysical and different in vitro actin-bundling assays confirm this activity. Subsequent assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. Furthermore, expression profiling suggests the activity of imipramine on the actin cytoskeleton. Moreover, in vivo studies using a zebrafish invasion model showed that imipramine is tolerated, its anti-invasive and antimetastatic activities are dose-dependent, and it is associated with both constitutive and induced fascin1 expression. This is the first study that demonstrates an antitumoral role of imipramine as a fascin1 inhibitor and constitutes a foundation for a molecular targeted therapy for SAC and other fascin1-overexpressing tumors.

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Section: Myoma Organotypic Invasion Modelmentioning

confidence: 99%

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Alburquerque-González

Bernabé-García

Montoro-García

et al. 2020

Exp Mol Med

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“…The filter of the Transwell-24 plate, pore size 8 µm (Corning) was coated with 50 µl of Myogel extracellular matrix developed in our laboratory (2.4 mg/ml of protein, 0.2% agarose in serum free culture medium) [14,15] and incubated at room temperature (RT) for 30 min. Next, 500 µl of normal medium containing the indicated amount of drugs was added in the bottom chambers.…”

Section: Invasion Assaymentioning

confidence: 99%

“…We have introduced a human 3D myoma disc organotypic model [12,13] and a gelatinous leiomyoma matrix, Myogel, for in vitro human cell invasion experiments [14,15]. 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].…”

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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“…This kind of in vitro models provides limited clinically relevant information. In 2D models, some key aspects like the impact of stroma and cell-to-cell interaction are lacking [38][39][40]. The effects of CAP have been reported to be highly dependent of the number of cells and 3D spatial distribution [41,42].…”

Section: Introductionmentioning

confidence: 99%

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Mateu-Sanz

Tornín

Brulin

et al. 2020

Cancers

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Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer’s saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.

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

Cited by 34 publications

References 89 publications

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

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

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

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