Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins

Abstract

Laminin-111 (Ln-1), an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells (MECs), dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks., thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7 to 1.8, whereas laminin-111 in neutral buffers formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. Finally, these findings support that the microstructure of Ln-1 networks in the basement membrane regulates mammary epithelial cell function.

Authors:
 [1];  [1];  [1];  [2];  [1];  [3]
+ Show Author Affiliations
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Texas Heart Inst., Houston, TX (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1760179
Alternate Identifier(s):
OSTI ID: 1564332
Report Number(s):
LLNL-JRNL-766544
Journal ID: ISSN 0142-9612; ark:/13030/qt44v5c2wx
Grant/Contract Number:  
AC02-05CH11231; AC52-07NA27344; BC133875; LDRD 18-ERD-062; NIH R01CA064786
Resource Type:
Accepted Manuscript
Journal Name:
Biomaterials
Additional Journal Information:
Journal Volume: 218; Journal ID: ISSN 0142-9612
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; laminin; dystroglycan; microstructure; mammary differentiation

Citation Formats

Kent, A. J., Mayer, N., Inman, J. L., Hochman-Mendez, C., Bissell, M. J., and Robertson, C. The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins. United States: N. p., 2019. Web. doi:10.1016/j.biomaterials.2019.119337.
Copy to clipboard
Kent, A. J., Mayer, N., Inman, J. L., Hochman-Mendez, C., Bissell, M. J., & Robertson, C. The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins. United States. https://doi.org/10.1016/j.biomaterials.2019.119337
Copy to clipboard
Kent, A. J., Mayer, N., Inman, J. L., Hochman-Mendez, C., Bissell, M. J., and Robertson, C. Tue . "The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins". United States. https://doi.org/10.1016/j.biomaterials.2019.119337. https://www.osti.gov/servlets/purl/1760179.
Copy to clipboard
@article{osti_1760179,
title = {The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins},
author = {Kent, A. J. and Mayer, N. and Inman, J. L. and Hochman-Mendez, C. and Bissell, M. J. and Robertson, C.},
abstractNote = {Laminin-111 (Ln-1), an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells (MECs), dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks., thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7 to 1.8, whereas laminin-111 in neutral buffers formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. Finally, these findings support that the microstructure of Ln-1 networks in the basement membrane regulates mammary epithelial cell function.},
doi = {10.1016/j.biomaterials.2019.119337},
journal = {Biomaterials},
number = ,
volume = 218,
place = {United States},
year = {Tue Jul 09 00:00:00 EDT 2019},
month = {Tue Jul 09 00:00:00 EDT 2019}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.biomaterials.2019.119337
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 4 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Laminin Polymerization Induces a Receptor–Cytoskeleton Network
journal, May 1999

  • Colognato, Holly; Winkelmann, Donald A.; Yurchenco, Peter D.
  • Journal of Cell Biology, Vol. 145, Issue 3
  • DOI: 10.1083/jcb.145.3.619

Form and function: The laminin family of heterotrimers
journal, May 2000

Laminin Polymerization Induces a Receptor–Cytoskeleton Network
journal, May 1999

  • Colognato, Holly; Winkelmann, Donald A.; Yurchenco, Peter D.
  • Journal of Cell Biology, Vol. 145, Issue 3
  • DOI: 10.1083/jcb.145.3.619

Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses
journal, November 1999

  • Côté, Patrice D.; Moukhles, Hakima; Lindenbaum, Michael
  • Nature Genetics, Vol. 23, Issue 3
  • DOI: 10.1038/15519

Multiscale analysis of collagen microstructure with generalized image correlation spectroscopy and the detection of tissue prestress
journal, August 2013

Heparin modulation of laminin polymerization.
journal, March 1990

Division of Labor among the α6β4 Integrin, β1 Integrins, and an E3 Laminin Receptor to Signal Morphogenesis and β-Casein Expression in Mammary Epithelial Cells
journal, September 1999

  • Muschler, John; Lochter, André; Roskelley, Calvin D.
  • Molecular Biology of the Cell, Vol. 10, Issue 9
  • DOI: 10.1091/mbc.10.9.2817

Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion.
journal, March 1985

  • Lee, E. Y.; Lee, W. H.; Kaetzel, C. S.
  • Proceedings of the National Academy of Sciences, Vol. 82, Issue 5
  • DOI: 10.1073/pnas.82.5.1419

Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses
journal, November 1999

  • Côté, Patrice D.; Moukhles, Hakima; Lindenbaum, Michael
  • Nature Genetics, Vol. 23, Issue 3
  • DOI: 10.1038/15519

Division of Labor among the α6β4 Integrin, β1 Integrins, and an E3 Laminin Receptor to Signal Morphogenesis and β-Casein Expression in Mammary Epithelial Cells
journal, September 1999

  • Muschler, John; Lochter, André; Roskelley, Calvin D.
  • Molecular Biology of the Cell, Vol. 10, Issue 9
  • DOI: 10.1091/mbc.10.9.2817

The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation
journal, September 2000

Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression
journal, March 2011

  • Bissell, Mina J.; Hines, William C.
  • Nature Medicine, Vol. 17, Issue 3
  • DOI: 10.1038/nm.2328

Self-assembly of Laminin Induced by Acidic pH
journal, January 2000

  • Freire, Elisabete; Coelho-Sampaio, Tatiana
  • Journal of Biological Chemistry, Vol. 275, Issue 2
  • DOI: 10.1074/jbc.275.2.817

Optical Imaging Predicts Mechanical Properties During Decellularization of Cardiac Tissue
journal, October 2013

  • Merna, Nick; Robertson, Claire; La, Anh
  • Tissue Engineering Part C: Methods, Vol. 19, Issue 10
  • DOI: 10.1089/ten.tec.2012.0720

Compound Genetic Ablation of Nidogen 1 and 2 Causes Basement Membrane Defects and Perinatal Lethality in Mice
journal, August 2005

Reduced expression of dystroglycan in breast and prostate cancer
journal, August 2001

  • Henry, Michael D.; Cohen, Michael B.; Campbell, Kevin P.
  • Human Pathology, Vol. 32, Issue 8
  • DOI: 10.1053/hupa.2001.26468

Recombinant Laminin-8 (α4β1γ1)
journal, May 2000

  • Kortesmaa, Jarkko; Yurchenco, Peter; Tryggvason, Karl
  • Journal of Biological Chemistry, Vol. 275, Issue 20
  • DOI: 10.1074/jbc.275.20.14853

Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells.
journal, January 1987

  • Li, M. L.; Aggeler, J.; Farson, D. A.
  • Proceedings of the National Academy of Sciences, Vol. 84, Issue 1
  • DOI: 10.1073/pnas.84.1.136

Laminin mediates tissue-specific gene expression in mammary epithelia
journal, May 1995

Laminin mediates tissue-specific gene expression in mammary epithelia
journal, May 1995

Dystroglycan does not contribute significantly to kidney development or function, in health or after injury
journal, March 2011

  • Jarad, George; Pippin, Jeffrey W.; Shankland, Stuart J.
  • American Journal of Physiology-Renal Physiology, Vol. 300, Issue 3
  • DOI: 10.1152/ajprenal.00725.2010

Radial viscous fingers and diffusion-limited aggregation: Fractal dimension and growth sites
journal, January 1986

  • Daccord, Gérard; Nittmann, Johann; Stanley, H. Eugene
  • Physical Review Letters, Vol. 56, Issue 4
  • DOI: 10.1103/PhysRevLett.56.336

Dystroglycan: Emerging Roles in Mammary Gland Function
journal, October 2003

Depletion of nuclear actin is a key mediator of quiescence in epithelial cells
journal, December 2010

  • Spencer, V. A.; Costes, S.; Inman, J. L.
  • Journal of Cell Science, Vol. 124, Issue 1
  • DOI: 10.1242/jcs.073197

Dystroglycan Is Essential for Early Embryonic Development: Disruption of Reichert's Membrane in Dag1-Null Mice
journal, June 1997

  • Williamson, Roger A.; Henry, Michael D.; Daniels, Karla J.
  • Human Molecular Genetics, Vol. 6, Issue 6
  • DOI: 10.1093/hmg/6.6.831

A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts
journal, March 2013

  • Martínez-Vieyra, Ivette A.; Vásquez-Limeta, Alejandra; González-Ramírez, Ricardo
  • Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1833, Issue 3
  • DOI: 10.1016/j.bbamcr.2012.11.019

A Fractal Nature for Polymerized Laminin
journal, October 2014

Direct interaction of β-dystroglycan with F-actin
journal, October 2003

  • Chen, Yun-Ju; Spence, Heather J.; Cameron, Jacqueline M.
  • Biochemical Journal, Vol. 375, Issue 2
  • DOI: 10.1042/bj20030808

Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity
journal, October 2010

  • Leonoudakis, D.; Singh, M.; Mohajer, R.
  • Journal of Cell Science, Vol. 123, Issue 21
  • DOI: 10.1242/jcs.070680

Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6
journal, June 2017

Recombinant Laminin-8 (α4β1γ1)
journal, May 2000

  • Kortesmaa, Jarkko; Yurchenco, Peter; Tryggvason, Karl
  • Journal of Biological Chemistry, Vol. 275, Issue 20
  • DOI: 10.1074/jbc.275.20.14853

Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer
journal, September 2013

  • Mathew, G.; Mitchell, A.; Down, J. M.
  • Scientific Reports, Vol. 3, Issue 1
  • DOI: 10.1038/srep02792

Dystroglycan does not contribute significantly to kidney development or function, in health or after injury
journal, March 2011

  • Jarad, George; Pippin, Jeffrey W.; Shankland, Stuart J.
  • American Journal of Physiology-Renal Physiology, Vol. 300, Issue 3
  • DOI: 10.1152/ajprenal.00725.2010

Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies
journal, April 1997

  • Weaver, V. M.; Petersen, O. W.; Wang, F.
  • The Journal of Cell Biology, Vol. 137, Issue 1
  • DOI: 10.1083/jcb.137.1.231

Theory and practical recommendations for autocorrelation-based image correlation spectroscopy
journal, August 2012

Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression
journal, March 2000

  • Pujuguet, P.; Simian, M.; Liaw, J.
  • Journal of Cell Science, Vol. 113, Issue 5
  • DOI: 10.1242/jcs.113.5.849
    Sort by:
    [ × clear filter / sort ]

    Similar Records in DOE PAGES and OSTI.GOV collections: