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Mechanisms of Disease: breast tumor pathogenesis and the role of the myoepithelial cell

Nature Clinical Practice Oncology volume 3, pages 138–151 (2006)Cite this article

Abstract

Breast cancer and precancer cells are influenced by important paracrine regulation from the breast microenvironment, which might be as great a determinant of breast cancer behavior as the specific oncogenic or tumor-suppressive alterations occurring within malignant breast cells. Myoepithelial cells exert profound effects on breast tumor cell behavior, and lie in juxtaposition to abnormally proliferating breast epithelial cells in precancerous disease states such as ductal carcinoma in situ (DCIS). Myoepithelial cells also form a natural border separating breast epithelial cells from stromal angiogenesis. These anatomical relationships suggest that myoepithelial cells might inhibit both the progression of DCIS to invasive breast cancer, and carcinoma-induced angiogenesis. Our ability to study myoepithelial cells has been fostered by recent technical advances in cell selection and sorting procedures, improved selective media, and high throughput technologies, which are able to assess the gene and protein expression profiles within cells. In addition, the establishment of a number of immortalized cell lines and xenografts of myoepithelial cells derived from benign human myoepithelial tumors of diverse sources has provided a self-renewing cell source through which to study the phenotype of myoepithelial cells. Studies of primary and immortalized myoepithelial cell lines indicate that these cells exhibit a natural tumor suppressor function. Functional studies show that these cells have anti-invasive and antiangiogenic phenotypes.

Key Points

  • Myoepithelial cells surround both normal ducts and precancerous lesions of the breast, and form a natural border separating epithelial cells from stromal cells

  • By forming this natural border, myoepithelial cells are thought to negatively regulate tumor invasion, angiogenesis and metastasis

  • Tumors of the myoepithelium are uncommon and usually benign, although highly aggressive malignant myoepitheliomas can occasionally occur, which have a poor prognosis

  • Myoepithelial cells function as both natural paracrine as well as autocrine tumor suppressors

  • Myoepithelial lines retain the ability to secrete and accumulate an abundant extracellular matrix containing both basement membrane and non-basement membrane components

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Figure 1: Myoepithelial cells surrounding breast ducts and acini are highlighted by differential maspin immunoreactivity.
Figure 2: Myoepithelial cells separate proliferating epithelial cells (left) from proliferating endothelial cells that characterize angiogenesis (right).
Figure 3: Maspin staining in myoepithelial cells.
Figure 4: Cytoplasmic maspin immunoreactivity of a typical myoepithelial xenograft recapitulates the strong maspin immunoreactivity of the normal myoepithelial cells, which is seen in Figure 1.
Figure 5: A typical myoepithelial xenograft, human matrix-secreting xenograft 4, has a well-circumscribed white cartilaginous appearance due to the abundance of extracellular matrix.
Figure 6: Morphology of a myoepithelial cell line.
Figure 7: Ultrastructural analysis of myoepithelial cells in culture shows abundant cytoplasm with numerous organelles and surface microvilli.
Figure 8: Microscopic analysis of human matrix-secreting xenograft 4.
Figure 9: Analysis of the density of vessels positive for von Willebrand factor in 10 high-power fields of myoepithelial versus nonmyoepithelial xenografts reveals significantly fewer blood vessels in myoepithelial xenografts.
Figure 10: Western blot of maspin demonstrating 42 kDa band (arrow) in ductal lavage fluid and in conditioned media from human matrix-secreting 1 myoepthelial cell cultures.
Figure 11: Gene expression profiling of cell samples using Affymetrix® (Affymetrix, Inc., Santa Clara, CA) technology.
Figure 12: Confirmation of the pattern of the gene expression of one prototype myoepithelial cell line (human matrix secreting 1, lane 1) compared with a prototype nonmyoepithelial carcinomatous cell line (lane 2).

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Acknowledgements

This work was supported by USPHS grants CA40225, CA01351 and CA71195, and Department of Defense grant DAMD17-00-1-0176, all of which were awarded to SH Barsky.

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Authors and Affiliations

  1. the Professor and Chairman of the Department of Pathology at The Ohio State University College of Medicine, Donald A Senhauser Endowed Chair of Pathology, Columbus, OH, USA

    Sanford H Barsky

  2. Board-Certified Internist at UCLA–Olive View Medical Center, Sylmar, CA, USA

    Nina J Karlin

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  1. Sanford H Barsky
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  2. Nina J Karlin
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Correspondence to Sanford H Barsky.

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Barsky, S., Karlin, N. Mechanisms of Disease: breast tumor pathogenesis and the role of the myoepithelial cell. Nat Rev Clin Oncol 3, 138–151 (2006). https://doi.org/10.1038/ncponc0450

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