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PMID: 16168137 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Myoepithelial cells: good fences make good neighbors.

Breast cancer research : BCR ·Vol. 7 ·No. 5 ·2005-00-00 ·Pages 190-7

Adriance MC, Inman JL, Petersen OW, Bissell MJ

Abstract

The mammary gland consists of an extensively branched ductal network contained within a distinctive basement membrane and encompassed by a stromal compartment. During lactation, production of milk depends on the action of the two epithelial cell types that make up the ductal network: luminal cells, which secrete the milk components into the ductal lumen; and myoepithelial cells, which contract to aid in the ejection of milk. There is increasing evidence that the myoepithelial cells also play a key role in the organizational development of the mammary gland, and that the loss and/or change of myoepithelial cell function is a key step in the development of breast cancer. In this review we briefly address the characteristics of breast myoepithelial cells from human breast and mouse mammary gland, how they function in normal mammary gland development, and their recently appreciated role in tumor suppression.

MeSH Terms
Animals Breast/cytology,physiology Breast Neoplasms/pathology,physiopathology,prevention & control Cell Polarity Epithelial Cells/cytology,physiology Female Humans Mice Reference Values
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Adriance Melissa C
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA. [email protected]
Inman Jamie L
Petersen Ole W
Bissell Mina J
References (103)
103 references, click to expand
  1. Stromal cell-derived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells.
    Mol Endocrinol. 2003 May;17(5):792-803 PMID: 12586845
  2. The role of laminin in embryonic cell polarization and tissue organization.
    Dev Cell. 2003 May;4(5):613-24 PMID: 12737798
  3. How to make tubes: signaling by the Met receptor tyrosine kinase.
    Trends Cell Biol. 2003 Jun;13(6):328-35 PMID: 12791299
  4. Breast cell invasive potential relates to the myoepithelial phenotype.
    Int J Cancer. 2003 Aug 10;106(1):8-16 PMID: 12794751
  5. Primary breast myoepithelial cells exert an invasion-suppressor effect on breast cancer cells via paracrine down-regulation of MMP expression in fibroblasts and tumour cells.
    J Pathol. 2003 Dec;201(4):562-72 PMID: 14648659
  6. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15853-8 PMID: 14668450
  7. Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation.
    Development. 2004 May;131(10):2247-56 PMID: 15102706
  8. Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma.
    Mod Pathol. 2004 Jun;17(6):646-52 PMID: 15073596
  9. Molecular characterization of the tumor microenvironment in breast cancer.
    Cancer Cell. 2004 Jul;6(1):17-32 PMID: 15261139
  10. Laminin functions in tissue morphogenesis.
    Annu Rev Cell Dev Biol. 2004;20:255-84 PMID: 15473841
  11. Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast.
    J Clin Pathol. 2004 Nov;57(11):1179-84 PMID: 15509680
  12. The myothelia (myoepithelial cells). Normal state; regressive changes; hyperplasia; tumors.
    Curr Top Pathol. 1970;53:161-220 PMID: 4323195
  13. Myoepithelial cell differentiation in rat mammary glands.
    J Anat. 1972 Apr;111(Pt 3):381-98 PMID: 4560931
  14. Cell contacts in the mouse mammary gland. I. Normal gland in postnatal development and the secretory cycle.
    J Cell Biol. 1973 Mar;56(3):797-818 PMID: 4569313
  15. The myoepithelium in human breast carcinoma.
    J Pathol. 1974 Jun;113(2):129-35 PMID: 4278826
  16. Intermediate-sized filaments of the prekeratin type in myoepithelial cells.
    J Cell Biol. 1980 Mar;84(3):633-54 PMID: 6153658
  17. Distribution of myoepithelial cells and basement membrane proteins in the resting, pregnant, lactating, and involuting rat mammary gland.
    J Histochem Cytochem. 1982 Jul;30(7):667-76 PMID: 6179984
  18. Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases.
    Cancer Res. 1982 Nov;42(11):4763-70 PMID: 6290045
  19. Monoclonal antibody that defines human myoepithelium.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7409-13 PMID: 2414776
  20. Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells.
    J Histochem Cytochem. 1986 Jul;34(7):869-81 PMID: 2423579
  21. Identification of myoepithelial cells in human and rat breasts by anti-common acute lymphoblastic leukemia antigen antibody A12.
    J Natl Cancer Inst. 1986 Aug;77(2):343-9 PMID: 2426509
  22. Cell size and shape changes in the myoepithelium of the mammary gland during differentiation.
    Anat Rec. 1986 Nov;216(3):405-15 PMID: 3789423
  23. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation.
    J Cell Biol. 1986 Dec;103(6 Pt 2):2787-96 PMID: 3539945
  24. Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor.
    Dev Biol. 1988 Jun;127(2):304-15 PMID: 3259938
  25. Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer.
    Int J Cancer. 1988 Aug 15;42(2):147-53 PMID: 2456993
  26. Characterization of human mammary cell types in primary culture: immunofluorescent and immunocytochemical indicators of cellular heterogeneity.
    In Vitro Cell Dev Biol. 1989 Jan;25(1):23-36 PMID: 2644183
  27. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane.
    Development. 1989 Feb;105(2):223-35 PMID: 2806122
  28. Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells.
    Proc Natl Acad Sci U S A. 1990 Mar;87(6):2314-8 PMID: 1690427
  29. Regulation of vimentin expression in cultured human mammary epithelial cells.
    Differentiation. 1990 Apr;43(2):146-56 PMID: 2373288
  30. Localization of basic fibroblast growth factor and transforming growth factor beta 1 in the human mammary gland.
    Cancer Res. 1991 Sep 1;51(17):4685-92 PMID: 1873813
  31. Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Correlations with their functions as receptors and cell adhesion molecules.
    Am J Pathol. 1991 Oct;139(4):787-99 PMID: 1928301
  32. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity.
    J Cell Biol. 1991 Dec;115(5):1383-95 PMID: 1955479
  33. Enhanced synthesis of gelatinase and stromelysin by myoepithelial cells during involution of the rat mammary gland.
    J Histochem Cytochem. 1992 May;40(5):697-703 PMID: 1315355
  34. Identification, paracrine generation, and possible function of human breast carcinoma myofibroblasts in culture.
    In Vitro Cell Dev Biol. 1992 Apr;28A(4):273-83 PMID: 1583005
  35. Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues.
    Int J Cancer. 1992 Jun 19;51(4):522-9 PMID: 1318266
  36. Monoclonal antibodies against laminin A chain fragment E3 and their effects on binding to cells and proteoglycan and on kidney development.
    Exp Cell Res. 1992 Jul;201(1):137-44 PMID: 1612119
  37. Changes in expression of alpha 6/beta 4 integrin heterodimer in primary and metastatic breast cancer.
    Br J Cancer. 1992 Aug;66(2):318-22 PMID: 1503905
  38. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9064-8 PMID: 1384042
  39. Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue.
    Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):999-1003 PMID: 8430113
  40. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition.
    J Cell Sci. 2002 Jan 1;115(Pt 1):39-50 PMID: 11801722
  41. Putting tumours in context.
    Nat Rev Cancer. 2001 Oct;1(1):46-54 PMID: 11900251
  42. Stromal effects on mammary gland development and breast cancer.
    Science. 2002 May 10;296(5570):1046-9 PMID: 12004111
  43. beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium.
    Cancer Cell. 2002 Sep;2(3):205-16 PMID: 12242153
  44. A role for dystroglycan in epithelial polarization: loss of function in breast tumor cells.
    Cancer Res. 2002 Dec 1;62(23):7102-9 PMID: 12460932
  45. Polarity determination in breast tissue: desmosomal adhesion, myoepithelial cells, and laminin 1.
    Breast Cancer Res. 2003;5(2):117-9 PMID: 12631393
  46. Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis.
    Dev Cell. 2003 Mar;4(3):371-82 PMID: 12636918
  47. Myoepithelial mRNA expression profiling reveals a common tumor-suppressor phenotype.
    Exp Mol Pathol. 2003 Apr;74(2):113-22 PMID: 12710942
  48. Distribution of tenascin, cellular fibronectins and integrins in the normal, hyperplastic and neoplastic breast.
    J Submicrosc Cytol Pathol. 1993 Apr;25(2):285-95 PMID: 7686813
  49. Identification by differential display of alpha 6 integrin as a candidate tumor suppressor gene.
    FASEB J. 1993 Jul;7(10):964-70 PMID: 8344495
  50. [Cytokeratins as markers of differentiation. Expression profiles in epithelia and epithelial tumors].
    Veroff Pathol. 1993;142:1-197 PMID: 7504860
  51. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.
    Science. 1994 Jan 28;263(5146):526-9 PMID: 8290962
  52. Differentiation of breast cancer cells in vitro is promoted by the concurrent influence of myoepithelial cells and relaxin.
    Br J Cancer. 1994 Nov;70(5):900-4 PMID: 7947095
  53. Antibodies against domain E3 of laminin-1 and integrin alpha 6 subunit perturb branching epithelial morphogenesis of submandibular gland, but by different modes.
    J Cell Biol. 1995 Apr;129(2):521-34 PMID: 7536749
  54. Laminin mediates tissue-specific gene expression in mammary epithelia.
    J Cell Biol. 1995 May;129(3):591-603 PMID: 7730398
  55. Expression and functional role of E- and P-cadherins in mouse mammary ductal morphogenesis and growth.
    Dev Biol. 1995 Jun;169(2):511-9 PMID: 7781895
  56. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma.
    J Cell Sci. 1995 May;108 ( Pt 5):1945-57 PMID: 7544798
  57. Extracellular matrix components in intestinal development.
    Experientia. 1995 Sep 29;51(9-10):883-900 PMID: 7556570
  58. HGF/SF: a potent cytokine for mammary growth, morphogenesis and development.
    Development. 1995 Sep;121(9):2897-908 PMID: 7555716
  59. Expression of hemidesmosomes and component proteins is lost by invasive breast cancer cells.
    Am J Pathol. 1995 Dec;147(6):1823-39 PMID: 7495306
  60. Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development.
    Development. 1995 Nov;121(11):3539-47 PMID: 8582268
  61. Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction.
    Physiol Rev. 1996 Jan;76(1):69-125 PMID: 8592733
  62. Characterizations of the extracellular matrix and proteinase inhibitor content of human myoepithelial tumors.
    Lab Invest. 1996 Apr;74(4):781-96 PMID: 8606488
  63. Gap junction distribution and connexin expression in human breast.
    Exp Cell Res. 1996 Feb 25;223(1):29-38 PMID: 8635493
  64. Inhibitory effects of activin on the growth and morpholgenesis of primary and transformed mammary epithelial cells.
    Cancer Res. 1996 Mar 1;56(5):1155-63 PMID: 8640777
  65. A function for filamentous alpha-smooth muscle actin: retardation of motility in fibroblasts.
    J Cell Biol. 1996 Jul;134(1):67-80 PMID: 8698823
  66. Growth factors and their receptors in neoplastic mammary glands.
    Biomed Pharmacother. 1995;49(9):389-99 PMID: 8746075
  67. Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential.
    Cell Growth Differ. 1996 Jul;7(7):861-70 PMID: 8809403
  68. Maspin acts at the cell membrane to inhibit invasion and motility of mammary and prostatic cancer cells.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11669-74 PMID: 8876194
  69. The molecular biology of axon guidance.
    Science. 1996 Nov 15;274(5290):1123-33 PMID: 8895455
  70. Expression genetics in cancer: shifting the focus from DNA to RNA.
    Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):952-5 PMID: 9023363
  71. A paracrine role for myoepithelial cell-derived FGF2 in the normal human breast.
    Exp Cell Res. 1997 Jul 10;234(1):165-73 PMID: 9223382
  72. Cellular distribution of the angiogenic factor heparin affin regulatory peptide (HARP) mRNA and protein in the human mammary gland.
    J Histochem Cytochem. 1997 Sep;45(9):1239-45 PMID: 9283611
  73. Precocious mammary gland development in P-cadherin-deficient mice.
    J Cell Biol. 1997 Nov 17;139(4):1025-32 PMID: 9362520
  74. Epimorphin functions as a key morphoregulator for mammary epithelial cells.
    J Cell Biol. 1998 Jan 12;140(1):159-69 PMID: 9425164
  75. Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells.
    Oncogene. 1998 Mar;16(11):1391-7 PMID: 9525738
  76. The human myoepithelial cell exerts antiproliferative effects on breast carcinoma cells characterized by p21WAF1/CIP1 induction, G2/M arrest, and apoptosis.
    Exp Cell Res. 1998 Jun 15;241(2):394-403 PMID: 9637781
  77. Cell-type specific and estrogen dependent expression of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 during mammary gland morphogenesis.
    J Cell Sci. 1998 Sep;111 ( Pt 18):2741-51 PMID: 9718367
  78. Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation.
    J Cell Biol. 1999 Jan 11;144(1):151-60 PMID: 9885251
  79. The human myoepithelial cell is a natural tumor suppressor.
    Clin Cancer Res. 1997 Nov;3(11):1949-58 PMID: 9815584
  80. Human mammary luminal epithelial cells contain progenitors to myoepithelial cells.
    Dev Biol. 1999 Feb 1;206(1):88-99 PMID: 9918697
  81. The induction of smooth muscle alpha actin in a transformed rat cell line suppresses malignant properties in vitro and in vivo.
    Cancer Lett. 1999 Aug 3;142(2):173-8 PMID: 10463773
  82. Division of labor among the alpha6beta4 integrin, beta1 integrins, and an E3 laminin receptor to signal morphogenesis and beta-casein expression in mammary epithelial cells.
    Mol Biol Cell. 1999 Sep;10(9):2817-28 PMID: 10473629
  83. The significance of focal myoepithelial cell layer disruptions in human breast tumor invasion: a paradigm shift from the "protease-centered" hypothesis.
    Exp Cell Res. 2004 Dec 10;301(2):103-18 PMID: 15530847
  84. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells.
    Breast Cancer Res. 2004;6(6):R605-15 PMID: 15535842
  85. CXCR4 regulates growth of both primary and metastatic breast cancer.
    Cancer Res. 2004 Dec 1;64(23):8604-12 PMID: 15574767
  86. Laminin alpha1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1502-6 PMID: 15668394
  87. Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma.
    J Pathol. 1993 Feb;169(2):245-50 PMID: 8383197
  88. Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast.
    Virchows Arch A Pathol Anat Histopathol. 1993;422(2):153-9 PMID: 8385380
  89. Immunocytochemical identification of basic fibroblast growth factor in the developing rat mammary gland: variations in location are dependent on glandular structure and differentiation.
    J Histochem Cytochem. 1993 Jun;41(6):887-98 PMID: 7686196
  90. Proteomic definition of normal human luminal and myoepithelial breast cells purified from reduction mammoplasties.
    Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12589-94 PMID: 10535966
  91. Form and function: the laminin family of heterotrimers.
    Dev Dyn. 2000 Jun;218(2):213-34 PMID: 10842354
  92. The mammary gland: a unique organ for the study of development and tumorigenesis.
    J Mammary Gland Biol Neoplasia. 1996 Jan;1(1):5-19 PMID: 10887477
  93. The human myoepithelial cell displays a multifaceted anti-angiogenic phenotype.
    Oncogene. 2000 Jul 20;19(31):3449-59 PMID: 10918603
  94. Molecular portraits of human breast tumours.
    Nature. 2000 Aug 17;406(6797):747-52 PMID: 10963602
  95. Involvement of chemokine receptors in breast cancer metastasis.
    Nature. 2001 Mar 1;410(6824):50-6 PMID: 11242036
  96. The mammary myoepithelial cell--Cinderella or ugly sister?
    Breast Cancer Res. 2001;3(1):1-4 PMID: 11250738
  97. Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta.
    J Cell Biol. 2001 May 14;153(4):785-94 PMID: 11352939
  98. Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue.
    Breast Cancer Res Treat. 2001 May;67(2):93-109 PMID: 11519870
  99. Desmosomal adhesion regulates epithelial morphogenesis and cell positioning.
    Nat Cell Biol. 2001 Sep;3(9):823-30 PMID: 11533662
  100. Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly.
    Nat Cell Biol. 2001 Sep;3(9):831-8 PMID: 11533663
  101. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells.
    Development. 2001 Aug;128(16):3117-31 PMID: 11688561
  102. Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase.
    J Cell Sci. 2002 Jan 1;115(Pt 1):25-37 PMID: 11801721
  103. Expression and biological role of laminin-1.
    Matrix Biol. 2003 Mar;22(1):35-47 PMID: 12714040
Article Info
Journal
Breast cancer research : BCR
Abbr.
Breast Cancer Res
ISSN
1465-542X
DOI
10.1186/bcr1286
Email
[email protected]
Published
2005-00-00
Epub
2005-00-12
Pages
190-7
Language
English
Region
England
NLM ID
100927353
PMCID
PMC1242144
Subset
IM
Grants
NCI NIH HHS · CA 64786 · United States
NCI NIH HHS · R37 CA064786 · United States
NCI NIH HHS · CA 57621 · United States
NCI NIH HHS · R01 CA057621 · United States
NCI NIH HHS · R01 CA064786 · United States
External Links
PubMed source DOI: 10.1186/bcr1286 PMC Full Text View journal details
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