Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An In-Vitro Approach to Model EMT in Breast Cancer

Version 1 : Received: 7 March 2023 / Approved: 8 March 2023 / Online: 8 March 2023 (06:29:48 CET)

A peer-reviewed article of this Preprint also exists.

Isert, L.; Mehta, A.; Loiudice, G.; Oliva, A.; Roidl, A.; Merkel, O.M. An In Vitro Approach to Model EMT in Breast Cancer. Int. J. Mol. Sci. 2023, 24, 7757. Isert, L.; Mehta, A.; Loiudice, G.; Oliva, A.; Roidl, A.; Merkel, O.M. An In Vitro Approach to Model EMT in Breast Cancer. Int. J. Mol. Sci. 2023, 24, 7757.

Abstract

During the progression from ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC), cells have to overcome the physically restraining basement membrane (BM) which compartmentalizes the epithelium from the stroma. Since the extracellular matrix (ECM) of the epithelial and stromal compartment is biochemically and physically distinct from one another, the progression demands a certain degree of cellular plasticity being essentially required for a primary tumor to become invasive. The Epithelial-to-Mesenchymal Transition depicts such a cell program equipping cancer cells with features allowing for dissemination from the epithelial entity and stromal invasion on the single-cell level. Here, we investigated the reciprocal interference between an altering tumor microenvironment and the EMT-phenotype in vitro. BM-typical collagen IV and stroma-typical collagen I coatings were applied as provisional 2-D matrices. Pro-inflammatory growth factors were introduced to improve tissue mimicry. Whereas the growth on coated surfaces did only slightly affect the EMT-phenotype, the combinatorial action of collagen with growth factor TGF-β1 induced prominent phenotypic changes. However, the EMT-induction was independent of the collagen type and cellular accessibility for EMT-like changes was strongly cell line dependent. Summarizing the entire body of data, we computed an EMT-phenotyping model that was used to decide on cellular EMT-status and estimate EMT-like changes. We confirmed that miR200c-mediated reversion of mesenchymal MDA-MB-231 cells is reflected by our EMT-phenotype model emphasizing its potential to predict the therapeutic efficacy of EMT-targeting drugs in the future.

Keywords

breast cancer; EMT; tumor microenvironment; collagen coatings; EMT-phenotyping; shape factors

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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