title: Increased extracellular matrix density decreases MCF10A breast cell acinus formation in 3D culture conditions.
abstract: The extracellular matrix (ECM) contributes to the generation and dynamic of normal breast tissue, in particular to the generation of polarized acinar and ductal structures. In vitro 3D culture conditions, including variations in the composition of the ECM, have been shown to directly influence the formation and organization of acinus-like and duct-like structures. Furthermore, the density of the ECM appears to also play a role in the normal mammary tissue and tumour formation. Here we show that the density of the ECM directly influences the number, organization and function of breast acini. Briefly, non-malignant human breast MCF10A cells were incubated in increasing densities of a Matrigel®-collagen I matrix. Elastic moduli near and distant to the acinus structures were measured by atomic force microscopy, and the number of acinus structures was determined. Immunochemistry was used to investigate the expression levels of E-cadherin, laminin, matrix metalloproteinase-14 and ß-casein in MCF10A cells. The modulus of the ECM was significantly increased near the acinus structures and the number of acinus structures decreased with the increase in Matrigel-collagen I density. As evaluated by the expression of laminin, the organization of the acinus structures present was altered as the density of the ECM increased. Increases in both E-cadherin and MMP14 expression by MCF10A cells as ECM density increased were also observed. In contrast, MCF10A cells expressed lower ß-casein levels as the ECM density increased. Taken together, these observations highlight the key role of ECM density in modulating the number, organization and function of breast acini.
authors: Cell and Molecular Division, Department of Biology, University of North Carolina, Charlotte, NC, USA.
authors: Amanda
authors: A
authors: Lance
authors: Department of Bioengineering, Clemson University, SC, USA.|Institute for Biological Interfaces of Engineering, Clemson University, SC, USA.
authors: Chih-Chao
authors: CC
authors: Yang
authors: Cell and Molecular Division, Department of Biology, University of North Carolina, Charlotte, NC, USA.
authors: Muthulekha
authors: M
authors: Swamydas
authors: Department of Bioengineering, Clemson University, SC, USA.|Institute for Biological Interfaces of Engineering, Clemson University, SC, USA.
authors: Delphine
authors: D
authors: Dean
authors: Department of Bioengineering, Clemson University, SC, USA.
authors: Sandy
authors: S
authors: Deitch
authors: Department of Bioengineering, Clemson University, SC, USA.|Institute for Biological Interfaces of Engineering, Clemson University, SC, USA.
authors: Karen J L
authors: KJ
authors: Burg
authors: Cell and Molecular Division, Department of Biology, University of North Carolina, Charlotte, NC, USA.|Institute for Biological Interfaces of Engineering, Clemson University, SC, USA.
authors: Didier
authors: D
authors: Dréau
mesh_terms: D061354:Acinar Cells / Q000166:cytology*; D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D048429:Cell Size; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D002364:Caseins; D007797:Laminin; D003094:Collagen; D053511:Matrix Metalloproteinase 14
keywords: E-cadherin; MMP14; acinus; breast; collagen; density; extracellular matrix; laminin; tensile strength; ß-casein