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

Journal Article · · Biomaterials
 [1];  [1];  [1];  [2];  [1];  [3]
  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)

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231; AC52-07NA27344
OSTI ID:
1760179
Alternate ID(s):
OSTI ID: 1564332
Report Number(s):
LLNL-JRNL--766544; ark:/13030/qt44v5c2wx
Journal Information:
Biomaterials, Journal Name: Biomaterials Vol. 218; ISSN 0142-9612
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

References (36)

Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses journal November 1999
Recombinant Laminin-8 (α4β1γ1) journal May 2000
Laminin mediates tissue-specific gene expression in mammary epithelia journal May 1995
Laminin Polymerization Induces a Receptor–Cytoskeleton Network journal May 1999
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
Radial viscous fingers and diffusion-limited aggregation: Fractal dimension and growth sites journal January 1986
Dystroglycan does not contribute significantly to kidney development or function, in health or after injury journal March 2011
Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high-throughput three-dimensional culture: example of the breast epithelium journal January 2009
Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development journal April 2004
Form and function: The laminin family of heterotrimers journal May 2000
Dystroglycan is not required for maintenance of the luminal epithelial basement membrane or cell polarity in the mouse prostate: Prostate-Specific Dystroglycan Knockout journal January 2010
Heparin modulation of laminin polymerization. journal March 1990
A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts journal March 2013
Multiscale analysis of collagen microstructure with generalized image correlation spectroscopy and the detection of tissue prestress journal August 2013
Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 journal June 2017
Ligand-binding specificities of laminin-binding integrins: A comprehensive survey of laminin–integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins journal April 2006
Dystroglycan: Emerging Roles in Mammary Gland Function journal October 2003
Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression journal March 2011
Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer journal September 2013
Direct interaction of β-dystroglycan with F-actin journal October 2003
Reduced expression of dystroglycan in breast and prostate cancer journal August 2001
Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion. journal March 1985
Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. journal January 1987
Self-assembly of Laminin Induced by Acidic pH journal January 2000
Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies journal April 1997
Optical Imaging Predicts Mechanical Properties During Decellularization of Cardiac Tissue journal October 2013
Dystroglycan Is Essential for Early Embryonic Development: Disruption of Reichert's Membrane in Dag1-Null Mice journal June 1997
Radial viscous fingers and diffusion-limited aggregation: Fractal dimension and growth sites journal January 1986
Theory and practical recommendations for autocorrelation-based image correlation spectroscopy journal August 2012
The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation journal September 2000
Compound Genetic Ablation of Nidogen 1 and 2 Causes Basement Membrane Defects and Perinatal Lethality in Mice journal August 2005
Dystroglycan loss disrupts polarity and  -casein induction in mammary epithelial cells by perturbing laminin anchoring journal October 2006
Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity journal October 2010
Depletion of nuclear actin is a key mediator of quiescence in epithelial cells journal December 2010
Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression journal March 2000
A Fractal Nature for Polymerized Laminin journal October 2014

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