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J. Clin. Med. 2019, 8(2), 213; https://doi.org/10.3390/jcm8020213

Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells

1
Department for Life Quality Studies, University of Bologna, Rimini 47100, Italy
2
Renal Unit, Department of Medicine, University Hospital of Verona, Verona 37100, Italy
3
Department of Biomedical Sciences, University of Padova, Padua 35100, Italy
4
Department of Pharmacy and Industrial Pharmacy, University of Bologna, Bologna 40100, Italy
5
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras 26110, Greece
Research has been conducted in collaboration and supervision by M.F.
*
Author to whom correspondence should be addressed.
Received: 27 December 2018 / Revised: 29 January 2019 / Accepted: 4 February 2019 / Published: 7 February 2019
(This article belongs to the Section Cell Biology)
Full-Text   |   PDF [5782 KB, uploaded 27 February 2019]   |  

Abstract

Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e., basement membrane, lamina propria under basement membrane, and deeper bundled collagen fibers with different array). These were used in 3D cell cultures to define their effects on morphology and behavior of breast cancer cells with different metastatic potential (MCF-7 and MDA-MB-231) using scanning electron microscope (SEM). We demonstrated that breast cancer cells cultured in 2D and 3D cultures on different collagen substrates show different morphologies: i) a globular/spherical shape, ii) a flattened polygonal shape, and iii) elongated/fusiform and spindle-like shapes. The distribution of different cell shapes changed with the distinct collagen fiber/fibril physical array and size. Dense collagen fibers, parallel to the culture plane, do not allow the invasion of MCF-7 and MDA-MB-231 cells, which, however, show increases of microvilli and microvesicles, respectively. These novel data highlight the regulatory role of different fibrillar collagen arrays in modifying breast cancer cell shape, inducing epithelial-to-mesenchymal transition, changing matrix composition and modulating the production of extracellular vesicles. Further investigation utilizing this in vitro model will help to demonstrate the biological roles of matrix macromolecules in cancer cell invasion in vivo. View Full-Text
Keywords: breast cancer; extracellular matrix; collagen type I; scanning electron microscope; epithelial-to-mesenchymal transition breast cancer; extracellular matrix; collagen type I; scanning electron microscope; epithelial-to-mesenchymal transition
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Franchi, M.; Masola, V.; Bellin, G.; Onisto, M.; Karamanos, K.-.A.; Piperigkou, Z. Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells. J. Clin. Med. 2019, 8, 213.

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