Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells.

Christine-Maria Horejs; Andrea Serio; Alan Purvis; Adam J Gormley; Sergio Bertazzo; Anna Poliniewicz; Alex J Wang; Peter DiMaggio; Erhard Hohenester; Molly M Stevens

doi:10.1073/pnas.1403139111

Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells.

Christine-Maria Horejs, Andrea Serio, Alan Purvis, Adam J Gormley, Sergio Bertazzo, Anna Poliniewicz, Alex J Wang, Peter DiMaggio, Erhard Hohenester, Molly M Stevens

Centre for Oral, Clinical & Translational Sciences

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59 Citations (Scopus)

Abstract

The dynamic interplay between the extracellular matrix and embryonic stem cells (ESCs) constitutes one of the key steps in understanding stem cell differentiation in vitro. Here we report a biologically-active laminin-111 fragment generated by matrix metalloproteinase 2 (MMP2) processing, which is highly up-regulated during differentiation. We show that the $1-chain-derived fragment interacts via $3$1-integrins, thereby triggering the down-regulation of MMP2 in mouse and human ESCs. Additionally, the expression of MMP9 and E-cadherin is up-regulated in mouse ESCs--key players in the epithelial-to-mesenchymal transition. We also demonstrate that the fragment acts through the $3$1-integrin/extracellular matrix metalloproteinase inducer complex. This study reveals a previously unidentified role of laminin-111 in early stem cell differentiation that goes far beyond basement membrane assembly and a mechanism by which an MMP2-cleaved laminin fragment regulates the expression of E-cadherin, MMP2, and MMP9.

Original language	English
Pages (from-to)	5908-5913
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	16
DOIs	https://doi.org/10.1073/pnas.1403139111
Publication status	Published - 1 Apr 2014

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Horejs, C.-M., Serio, A., Purvis, A., Gormley, A. J., Bertazzo, S., Poliniewicz, A., Wang, A. J., DiMaggio, P., Hohenester, E., & Stevens, M. M. (2014). Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 111(16), 5908-5913. https://doi.org/10.1073/pnas.1403139111

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title = "Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells.",

abstract = "The dynamic interplay between the extracellular matrix and embryonic stem cells (ESCs) constitutes one of the key steps in understanding stem cell differentiation in vitro. Here we report a biologically-active laminin-111 fragment generated by matrix metalloproteinase 2 (MMP2) processing, which is highly up-regulated during differentiation. We show that the $1-chain-derived fragment interacts via $3$1-integrins, thereby triggering the down-regulation of MMP2 in mouse and human ESCs. Additionally, the expression of MMP9 and E-cadherin is up-regulated in mouse ESCs--key players in the epithelial-to-mesenchymal transition. We also demonstrate that the fragment acts through the $3$1-integrin/extracellular matrix metalloproteinase inducer complex. This study reveals a previously unidentified role of laminin-111 in early stem cell differentiation that goes far beyond basement membrane assembly and a mechanism by which an MMP2-cleaved laminin fragment regulates the expression of E-cadherin, MMP2, and MMP9.",

author = "Christine-Maria Horejs and Andrea Serio and Alan Purvis and Gormley, {Adam J} and Sergio Bertazzo and Anna Poliniewicz and Wang, {Alex J} and Peter DiMaggio and Erhard Hohenester and Stevens, {Molly M}",

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doi = "10.1073/pnas.1403139111",

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Horejs, C-M, Serio, A, Purvis, A, Gormley, AJ, Bertazzo, S, Poliniewicz, A, Wang, AJ, DiMaggio, P, Hohenester, E & Stevens, MM 2014, 'Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells.', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 16, pp. 5908-5913. https://doi.org/10.1073/pnas.1403139111

Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells. / Horejs, Christine-Maria; Serio, Andrea; Purvis, Alan et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 16, 01.04.2014, p. 5908-5913.

Research output: Contribution to journal › Article › peer-review

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T1 - Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells.

AU - Horejs, Christine-Maria

AU - Serio, Andrea

AU - Purvis, Alan

AU - Gormley, Adam J

AU - Bertazzo, Sergio

AU - Poliniewicz, Anna

AU - Wang, Alex J

AU - DiMaggio, Peter

AU - Hohenester, Erhard

AU - Stevens, Molly M

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AB - The dynamic interplay between the extracellular matrix and embryonic stem cells (ESCs) constitutes one of the key steps in understanding stem cell differentiation in vitro. Here we report a biologically-active laminin-111 fragment generated by matrix metalloproteinase 2 (MMP2) processing, which is highly up-regulated during differentiation. We show that the $1-chain-derived fragment interacts via $3$1-integrins, thereby triggering the down-regulation of MMP2 in mouse and human ESCs. Additionally, the expression of MMP9 and E-cadherin is up-regulated in mouse ESCs--key players in the epithelial-to-mesenchymal transition. We also demonstrate that the fragment acts through the $3$1-integrin/extracellular matrix metalloproteinase inducer complex. This study reveals a previously unidentified role of laminin-111 in early stem cell differentiation that goes far beyond basement membrane assembly and a mechanism by which an MMP2-cleaved laminin fragment regulates the expression of E-cadherin, MMP2, and MMP9.

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JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells.

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