MCF7 Spheroid Development: New Insight about Spatio/Temporal Arrangements of TNTs, Amyloid Fibrils, Cell Connections, and Cellular Bridges.

Pulze, Laura; Congiu, Terenzio; Brevini, Tiziana A L; Grimaldi, Annalisa; Tettamanti, Gianluca; D'Antona, Paola; Baranzini, Nicolò; Acquati, Francesco; Ferraro, Federico; de Eguileor, Magda

Pulze, Laura; Congiu, Terenzio; Brevini, Tiziana A L; Grimaldi, Annalisa; Tettamanti, Gianluca; D'Antona, Paola; Baranzini, Nicolò; Acquati, Francesco; Ferraro, Federico; de Eguileor, Magda.

Afiliación

Pulze L; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
Congiu T; Department of Surgical Science, University of Cagliari, via Università 40, 09124 Cagliari, Italy.
Brevini TAL; Laboratory of Biomedical Embryology, Centre for Stem Cell research, University of Milan, via Celoria 10, 20133 Milan, Italy.
Grimaldi A; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
Tettamanti G; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
D'Antona P; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
Baranzini N; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
Acquati F; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
Ferraro F; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
de Eguileor M; Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.

Int J Mol Sci ; 21(15)2020 Jul 29.

Article en En | MEDLINE | ID: mdl-32751344

RESUMEN

Human breast adenocarcinoma cells (MCF7) grow in three-dimensional culture as spheroids that represent the structural complexity of avascular tumors. Therefore, spheroids offer a powerful tool for studying cancer development, aggressiveness, and drug resistance. Notwithstanding the large amount of data regarding the formation of MCF7 spheroids, a detailed description of the morpho-functional changes during their aggregation and maturation is still lacking. In this study, in addition to the already established role of gap junctions, we show evidence of tunneling nanotube (TNT) formation, amyloid fibril production, and opening of large stable cellular bridges, thus reporting the sequential events leading to MCF7 spheroid formation. The variation in cell phenotypes, sustained by dynamic expression of multiple proteins, leads to complex networking among cells similar to the sequence of morphogenetic steps occurring in embryogenesis/organogenesis. On the basis of the observation that early events in spheroid formation are strictly linked to the redox homeostasis, which in turn regulate amyloidogenesis, we show that the administration of N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger that reduces the capability of cells to produce amyloid fibrils, significantly affects their ability to aggregate. Moreover, cells aggregation events, which exploit the intrinsic adhesiveness of amyloid fibrils, significantly decrease following the administration during the early aggregation phase of neutral endopeptidase (NEP), an amyloid degrading enzyme.

Asunto(s)

Acetilcisteína/farmacología; Amiloide/química; Depuradores de Radicales Libres/farmacología; Uniones Comunicantes/ultraestructura; Homeostasis/efectos de los fármacos; Esferoides Celulares/ultraestructura; Amiloide/efectos de los fármacos; Amiloide/metabolismo; Biomarcadores de Tumor/genética; Biomarcadores de Tumor/metabolismo; Agregación Celular/efectos de los fármacos; Conexina 43/genética; Conexina 43/metabolismo; Uniones Comunicantes/efectos de los fármacos; Uniones Comunicantes/metabolismo; Expresión Génica; Homeostasis/genética; Humanos; Interleucina-18/genética; Interleucina-18/metabolismo; Células MCF-7; Neprilisina/farmacología; Oxidación-Reducción; Fenotipo; Proteolisis; Especies Reactivas de Oxígeno/antagonistas & inhibidores; Especies Reactivas de Oxígeno/metabolismo; Factores de Transcripción SOXB1/genética; Factores de Transcripción SOXB1/metabolismo; Esferoides Celulares/efectos de los fármacos; Esferoides Celulares/metabolismo; Antígenos Embrionarios Específico de Estadio/genética; Antígenos Embrionarios Específico de Estadio/metabolismo; Factores de Transcripción/genética; Factores de Transcripción/metabolismo; Antígeno gp100 del Melanoma/genética; Antígeno gp100 del Melanoma/metabolismo

Palabras clave

MCF7 3D spheroid; NEP treatment; ROS scavenger; TNTs; amyloid fibrils; cytoplasmic bridges; gap junctions

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcisteína / Depuradores de Radicales Libres / Uniones Comunicantes / Esferoides Celulares / Homeostasis / Amiloide Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza

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