Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1993 Feb 1; 90(3): 999–1003.

Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue.


The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts ("myofibroblasts") associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections. Several antibodies to smooth muscle-specific proteins (smooth muscle alpha-actin, smooth muscle myosin heavy chains, calponin, alpha 1-integrin, and high molecular weight caldesmon) and to epithelial-specific proteins (cytokeratins, E-cadherin, and desmoplakin) were used to show that myoepithelial cells concomitantly express epithelial and smooth muscle markers whereas adjacent luminal cells express only epithelial markers. The same antibodies were used to establish that stromal myofibroblasts exhibit smooth muscle phenotypic properties characterized by the expression of all the smooth muscle markers examined except for high molecular weight caldesmon. In addition, both myoepithelium and myofibroblasts show a significant degree of heterogeneity in smooth muscle protein expression. Thus, myoepithelial cells and stromal myofibroblasts are epithelial and mesenchymal cells, respectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features. The dual nature of myoepithelial cells and the phenotypic transition of fibroblasts to myofibroblasts are examples of the plasticity of the differentiated cell phenotype.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Blau HM, Baltimore D. Differentiation requires continuous regulation. J Cell Biol. 1991 Mar;112(5):781–783. [PMC free article] [PubMed]
  • Blau HM, Pavlath GK, Hardeman EC, Chiu CP, Silberstein L, Webster SG, Miller SC, Webster C. Plasticity of the differentiated state. Science. 1985 Nov 15;230(4727):758–766. [PubMed]
  • Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, Blackwell TK, Turner D, Rupp R, Hollenberg S, et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. [PubMed]
  • Gown AM. The mysteries of the myofibroblast (partially) unmasked. Lab Invest. 1990 Jul;63(1):1–3. [PubMed]
  • Sappino AP, Schürch W, Gabbiani G. Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest. 1990 Aug;63(2):144–161. [PubMed]
  • Gugliotta P, Sapino A, Macrí L, Skalli O, Gabbiani G, Bussolati G. Specific demonstration of myoepithelial cells by anti-alpha smooth muscle actin antibody. J Histochem Cytochem. 1988 Jun;36(6):659–663. [PubMed]
  • Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986 Dec;103(6 Pt 2):2787–2796. [PMC free article] [PubMed]
  • Gown AM, Vogel AM, Gordon D, Lu PL. A smooth muscle-specific monoclonal antibody recognizes smooth muscle actin isozymes. J Cell Biol. 1985 Mar;100(3):807–813. [PMC free article] [PubMed]
  • Longtine JA, Pinkus GS, Fujiwara K, Corson JM. Immunohistochemical localization of smooth muscle myosin in normal human tissues. J Histochem Cytochem. 1985 Mar;33(3):179–184. [PubMed]
  • Belkin VM, Belkin AM, Koteliansky VE. Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development. J Cell Biol. 1990 Nov;111(5 Pt 1):2159–2170. [PMC free article] [PubMed]
  • Glukhova MA, Kabakov AE, Ornatsky OI, Vasilevskaya TD, Koteliansky VE, Smirnov VN. Immunoreactive forms of caldesmon in cultivated human vascular smooth muscle cells. FEBS Lett. 1987 Jun 29;218(2):292–294. [PubMed]
  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. [PubMed]
  • Troyanovsky SM, Guelstein VI, Tchipysheva TA, Krutovskikh VA, Bannikov GA. Patterns of expression of keratin 17 in human epithelia: dependency on cell position. J Cell Sci. 1989 Jul;93(Pt 3):419–426. [PubMed]
  • Boyer B, Thiery JP. Epithelial cell adhesion mechanisms. J Membr Biol. 1989 Dec;112(2):97–108. [PubMed]
  • Hemler ME, Sanchez-Madrid F, Flotte TJ, Krensky AM, Burakoff SJ, Bhan AK, Springer TA, Strominger JL. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. J Immunol. 1984 Jun;132(6):3011–3018. [PubMed]
  • Shimoyama Y, Hirohashi S, Hirano S, Noguchi M, Shimosato Y, Takeichi M, Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed]
  • Frid MG, Shekhonin BV, Koteliansky VE, Glukhova MA. Phenotypic changes of human smooth muscle cells during development: late expression of heavy caldesmon and calponin. Dev Biol. 1992 Oct;153(2):185–193. [PubMed]
  • Kawamoto S, Adelstein RS. Characterization of myosin heavy chains in cultured aorta smooth muscle cells. A comparative study. J Biol Chem. 1987 May 25;262(15):7282–7288. [PubMed]
  • Franke WW, Schmid E, Freudenstein C, Appelhans B, Osborn M, Weber K, Keenan TW. Intermediate-sized filaments of the prekeratin type in myoepithelial cells. J Cell Biol. 1980 Mar;84(3):633–654. [PMC free article] [PubMed]
  • Gown AM, Boyd HC, Chang Y, Ferguson M, Reichler B, Tippens D. Smooth muscle cells can express cytokeratins of "simple" epithelium. Immunocytochemical and biochemical studies in vitro and in vivo. Am J Pathol. 1988 Aug;132(2):223–232. [PMC free article] [PubMed]
  • Glukhova MA, Shekhonin BV, Kruth H, Koteliansky VE. Expression of cytokeratin 8 in human aortic smooth muscle cells. Am J Physiol. 1991 Oct;261(4 Suppl):72–77. [PubMed]
  • Jahn L, Franke WW. High frequency of cytokeratin-producing smooth muscle cells in human atherosclerotic plaques. Differentiation. 1989 Mar;40(1):55–62. [PubMed]
  • Glukhova MA, Kabakov AE, Frid MG, Ornatsky OI, Belkin AM, Mukhin DN, Orekhov AN, Koteliansky VE, Smirnov VN. Modulation of human aorta smooth muscle cell phenotype: a study of muscle-specific variants of vinculin, caldesmon, and actin expression. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9542–9546. [PMC free article] [PubMed]
  • Sappino AP, Skalli O, Jackson B, Schürch W, Gabbiani G. Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues. Int J Cancer. 1988 May 15;41(5):707–712. [PubMed]
  • Darby I, Skalli O, Gabbiani G. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest. 1990 Jul;63(1):21–29. [PubMed]
  • Cintorino M, Bellizzi de Marco E, Leoncini P, Tripodi SA, Xu LJ, Sappino AP, Schmitt-Gräff A, Gabbiani G. Expression of alpha-smooth-muscle actin in stromal cells of the uterine cervix during epithelial neoplastic changes. Int J Cancer. 1991 Apr 1;47(6):843–846. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...