Mesenchymal-epithelial transition reduces proliferation but increases immune evasion in tumor spheroids

Dimari, Gina; Hu, Yueyuan; Frenzel, Annika; Fuchs, Anke; Wurm, Alexander A.; Fischer-Friedrich, Elisabeth

Mesenchymal-epithelial transition reduces proliferation but increases immune evasion in tumor spheroids

Type of the data datacite.resourceTypeGeneral	Collection
Total size of the dataset datacite.size	670441950960
Author dc.contributor.author	Dimari, Gina
Author dc.contributor.author	Hu, Yueyuan
Author dc.contributor.author	Frenzel, Annika
Author dc.contributor.author	Fuchs, Anke
Author dc.contributor.author	Wurm, Alexander A.
Author dc.contributor.author	Fischer-Friedrich, Elisabeth
Upload date dc.date.accessioned	2025-05-23T11:57:55Z
Publication date dc.date.available	2025-05-23T11:57:55Z
Publication date dc.date.issued	2025-05-23
Abstract of the dataset dc.description.abstract	The data corresponds to experiments performed with MET-inducible models of MDA-MB-231 and ES-2 mesenchymal cell lines. These were modified to contain an inducible plasmid that codes for miR-200c and miR-141 that upon overexpression trigger the expression of epithelial features. In the first place, the collection contains transcriptomic and proteomic data suchs as RNA seq data, q-PCR data, western-blot data, and immunofluorescence of EMT markers, that were all used to characterize our models. Moving forwards, with these two models we performed proliferation assays in adherent and 3D cultures of different nature. In adherent cultures, we looked at the effect of MET on proliferation focusing on the regulation exhorted by mechanical signals such as cell-cell junctions, spread area and their influence on contact inhibition of proliferation. Most of the data acquired from these experiments were obtained by image analysis of immunofluorescent microscopy. To measure proliferation changes in 3D cultures, we cultured cells in PEG-heparin hydrogels at both degradable and non-degradable forms. This gave rise to tumor spheroids were we quantified different parameters to assess proliferation levels. Moreover, we used pharmacologycal inhibitors to study the effect of focal adhesion and actomyosin cytoskeletal signaling in the proliferation of these tumor spheroids, culture in control and MET-inducing conditions. The data from these experiments was as well obtained from image analysis from fluorescent microscopy. Furthermore, we performed co-cultures of tumor spheroids with peripheral blood mononuclear cells and quantified the changes in apoptosis in the tumor cells, both by image analysis from immunofluorescent microscopy and flow cytometry.
Public reference to this page dc.identifier.uri	https://opara.zih.tu-dresden.de/handle/123456789/1458
Public reference to this page dc.identifier.uri	https://doi.org/10.25532/OPARA-832
Publisher dc.publisher	Technische Universität Dresden
Licence dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 International	en
URI of the licence text dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
Specification of the discipline(s) dc.subject.classification	3
Title of the dataset dc.title	Mesenchymal-epithelial transition reduces proliferation but increases immune evasion in tumor spheroids
Project abstract opara.project.description	The mesenchymal-epithelial transition (MET), whether full or partial, has been implicated in secondary tumor growth during metastasis, yet the underlying mechanisms remain unclear. Here, we explore whether MET enhances tumor outgrowth by boosting proliferation, using MET-inducible mesenchymal breast cancer cells. Surprisingly, we found that crowding inhibition of proliferation persists both before and after MET, with mesenchymal cells exhibiting a proliferative edge through more effective escape from crowded cell islands. In three-dimensional culture, MET caused a reduction in proliferation, accompanied by distinct changes in proliferative signaling of focal adhesions and actomyosin. Interestingly, Src-inhibited spheroids showed enhanced proliferation upon MET. Furthermore, co-culture experiments with peripheral blood mononuclear cells reveal that MET-induced spheroids demonstrate an increased ability to evade immune cell attacks. This effect is likely mediated by both the confined epithelial morphology and alterations in the expression of key immunomodulatory molecules. Together, these findings suggest that MET may contribute to secondary tumor outgrowth, not by boosting proliferation, but by enhancing survival in immune-challenging environments.
Project title opara.project.title	Mesenchymal-epithelial transition reduces proliferation but increases immune evasion in tumor spheroids