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beta 1 Integrins restrict the growth of foci and spheroids
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Staffan Johansson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Staffan Johansson)
2012 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 138, no 6, 881-894 p.Article in journal (Refereed) Published
Abstract [en]

Extracellular matrices (ECM) have important roles for tissue architecture, both as structural and signaling components. Members of the integrin family are the main regulators of ECM assembly and transmitters of signals from the ECM to cells. In this study, we have analyzed the role of integrin subunit beta 1 in two-dimensional (2D) and three-dimensional (3D) cell cultures using integrin beta 1 null cells (MEF beta 1(-/-) and GD25) and their beta 1 integrin-expressing counterparts. GD25 and GD25 beta 1 cells proliferated with similar kinetics in sub-confluent 2D cultures, whereas GD25 cells attained higher cell numbers in confluent culture and formed foci with fivefold higher frequency than GD25 beta 1 cells. Fibronectin fibrils were abundantly deposited throughout the GD25 beta 1 colonies but strictly limited to the central multilayered area (focus) of GD25 colonies. During 3D growth as spheroids, GD25 continuously increased in size for > 21 days while the growth of GD25 beta 1 spheroids ceased after 14 days. Similarly, MEF beta 1(-/-) cells formed foci and grew as spheroids, while the beta 1 integrin-expressing MEF did not. Expression levels of the cell cycle markers Ki67, PCNA, and histone H3-pSer10 were similar between GD25 beta 1 and GD25 spheroids. Apoptotic cells accumulated earlier in GD25 spheroids; however, cell death increased with spheroid volumes in both spheroid types. In both cell systems, the presence of beta 1 integrins resulted in higher levels of active myosin light chain and inactive myosin light chain phosphatase, and a more compact spheroid structure. In conclusion, our results reveal that regulation of 3D growth in spheroids and foci is dependent on the beta 1 subfamily of integrins, and suggest that myosin-based spheroid contraction in combination with cell death limits the growth of beta 1-expressing spheroids.

Place, publisher, year, edition, pages
2012. Vol. 138, no 6, 881-894 p.
Keyword [en]
Spheroid, Focus formation, Integrin, Fibronectin, Extracellular matrix, 2-Dimensional culture, 3-Dimensional culture, GD25 cells
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-187006DOI: 10.1007/s00418-012-1003-7ISI: 000310384900005OAI: oai:DiVA.org:uu-187006DiVA: diva2:573656
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2016-01-17

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Gupta, Rajesh KumarJohansson, Staffan
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