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<title lang=en>Increasing 3D Matrix Rigidity Strengthens Proliferation and Spheroid Development of Human Liver Cells in a Constant Growth Factor Environment</title>
<creator>Bomo, Jérémy</creator>
<creator>Ezan, Frédéric</creator>
<creator>Tiaho, François</creator>
<creator>Bellamri, Medjda</creator>
<creator>Langouët, Sophie</creator>
<creator>Théret, Nathalie</creator>
<creator>Baffet, Georges</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor> Institut National de la Santé et de la Recherche Médicale (Inserm) Université de Rennes 1 Ligue contre le cancer du Grand Ouest ANSES National EST-13-166 program and Région Bretagne Ministère de l'Enseignement Supérieur et de la Recherche Région Bretagne</contributor>
<description>International audience</description>
<source>ISSN: 0730-2312</source>
<source>EISSN: 1097-4644</source>
<source>Journal of Cellular Biochemistry</source>
<publisher>Wiley</publisher>
<identifier>hal-01196600</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600/document</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600/file/Increasing%203D%20Matrix%20Rigidity_accepted.pdf</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600</source>
<source>Journal of Cellular Biochemistry, Wiley, 2016, 117 (3), pp.708-720. 〈10.1002/jcb.25356〉</source>
<identifier>DOI : 10.1002/jcb.25356</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/jcb.25356</relation>
<identifier>PUBMED : 26331987</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/26331987</relation>
<language>en</language>
<subject lang=en>liver cells</subject>
<subject lang=en>proliferation</subject>
<subject lang=en>biotransformation</subject>
<subject lang=en>Matrix stiffness</subject>
<subject>[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Mechanical forces influence the growth and shape of virtually all tissues and organs. Recent studies show that increased cell contractibility, growth and differentiation might be normalized by modulating cell tensions. Particularly, the role of these tensions applied by the extracellular matrix during liver fibrosis could influence the hepatocarcinogenesis process. The objective of this study is to determine if 3D stiffness could influence growth and phenotype of normal and transformed hepatocytes and to integrate extracellular matrix (ECM) stiffness to tensional homeostasis. We have developed an appropriate 3D culture model: hepatic cells within three-dimensional collagen matrices with varying rigidity. Our results demonstrate that the rigidity influenced the cell phenotype and induced spheroid clusters development whereas in soft matrices, Huh7 transformed cells were less proliferative, well-spread and flattened. We confirmed that ERK1 played a predominant role over ERK2 in cisplatin-induced death, whereas ERK2 mainly controlled proliferation. As compared to 2D culture, 3D cultures are associated with epithelial markers expression. Interestingly, proliferation of normal hepatocytes was also induced in rigid gels. Furthermore, biotransformation activities are increased in 3D gels, where CYP1A2 enzyme can be highly induced/activated in primary culture of human hepatocytes embedded in the matrix. In conclusion, we demonstrated that increasing 3D rigidity could promote proliferation and spheroid developments of liver cells demonstrating that 3D collagen gels are an attractive tool for studying rigidity-dependent homeostasis of the liver cells embedded in the matrix and should be privileged for both chronic toxicological and pharmacological drug screening.</description>
<date>2016</date>
</dc>
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