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In search of mammary gland stem cells

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Summary

The evidence for mammary epithelial stem cells and their phenotypic characteristics in normal and neoplastic development is reviewed. The presence of stem cells in all parts of the mammary parenchyma at all stages of differentiation has been demonstrated by transplantation experiments. The phenotypic characterization of stem cells has been defined by a battery of monospecific antibodies. These studies suggest that a mammary epithelium stem cell compartment exists in the basal layer of the gland as well as in the end bud. Whether these same stem cells are expressed in mammary preneoplasias and neoplasias has not been answered conclusively. Phenotypic markers specific for stem cells and stably expressed in transformed cell populations are needed to follow the fate of stem cells.

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References

  • Allen R, Dulbecco R, Syka P, Bowman M, Armstrong B (1984) Developmental regulation of cytokeratins in cells of the rat mammary gland studied with monoclonal antibodies. Proc Natl Acad Sci USA 81: 1203–1207

    Google Scholar 

  • Barraclough R, Rudland PS (1989) Differentiation of mammary stem cells in vivo and in vitro. Environ Health Perspect 80: 39–48

    Google Scholar 

  • Bennett DC, Peachey LA, Durbin H, Rudland PS (1978) A possible mammary stem cell line. Cell 15: 283–298

    Google Scholar 

  • Berger JJ, Daniel CW (1983) Stromal DNA synthesis is stimulated by young, but not serially aged, mouse mammary epithelium. Mech Ageing Dev 23: 277–284

    Google Scholar 

  • Campbell SM, Taha MM, Medina D, Rosen J (1988) A clonal derivative of mammary epithelial cell line COMMA-D retains stem cell characteristics of unique morphological and functional heterogeneity. Exp Cell Res 177: 109–121

    Google Scholar 

  • Cardiff RD (1984) Protoneoplasia: the molecular biology of murine mammary hyperplasia. Adv Cancer Res 42: 167–190

    Google Scholar 

  • —, Morris DW, Young LJT (1983) Alterations of acquired mouse mammary tumor virus DNA during mammary tumorigenesis in BALB/cfC3H mice. J Natl Cancer Inst 71: 1011–1019

    Google Scholar 

  • Coleman S, Silberstein GB, Daniel CW (1988) Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor. Dev Biol 127: 304–315

    Google Scholar 

  • Daams J, Sonnenberg A, Sakakura T, Hilgers J (1987) Changes in antigen patterns during development of the mouse mammary gland: implications for tumorigenesis. In: Medina D, Kidwell W, Heppner G, Anderson E (eds) Cellular and molecular biology of mammary cancer. Plenum, New York, pp 1–8

    Google Scholar 

  • Daniel DW, Silberstein GB (1987) Postnatal development of the rodent mammary gland. In: Neville MC, Daniel CW (eds) The mammary gland. Plenum, New York, pp 3–36

    Google Scholar 

  • —, Young LJT (1971) Influence of cell division on an aging process. Exp Cell Res 65: 27–32

    Google Scholar 

  • —, DeOme KB, Young LJT, Blair PB, Faulkin LJ Jr (1968) The in vivo lifespan of normal and preneoplastic mouse mammary glands: a serial transplantation study. Proc Natl Acad Sci USA 61: 52–60

    Google Scholar 

  • —, Silberstein GB, Strickland P (1987) Direct action of 17β-estradiol on mouse mammary ducts analyzed by sustained release implants and steroid autoradiography. Cancer Res 47: 6052–6057

    Google Scholar 

  • Danielson KG, Oborn CJ, Durban EM, Butel JS, Medina D (1984) An epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro. Proc Natl Acad Sci USA 81: 3756–3760

    Google Scholar 

  • —, Knepper JE, Kittrell FS, Butel JS, Medina D, Durban EM (1989) Clonal populations of the mouse mammary cell line, COMMA-D, which retain capability of morphogenesis in vivo. In Vitro Cell Dev Biol 25: 535–543

    Google Scholar 

  • DeOme KB, Faulkin LJ Jr, Bern HA (1959) Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res 19: 515–520

    Google Scholar 

  • Dulbecco R, Henahan M, Armstrong B (1982) Cell types and morphogenesis in the mammary gland. Proc Natl Acad Sci USA 79: 7346–7350

    Google Scholar 

  • —, Unger M, Armstrong B, Bowman M, Syka P (1983) Epithelial cell types and their evolution in the rat mammary gland determined by immunological markers. Proc Natl Acad Sci USA 80: 1033–1037

    Google Scholar 

  • —, Allen WR, Bologna M, Bowman M (1986) Marker evolution during the development of the rat mammary gland: stem cells identified by markers and the role of myoepithelial cells. Cancer Res 46: 2449–2456

    Google Scholar 

  • Faulkin LJ Jr, De Ome KB (1960) Regulation of growth and spacing of gland elements in the mammary fat pad of the C3H mouse. J Natl Cancer Inst 24: 953–969

    Google Scholar 

  • Haslam SZ (1986) Mammary fibroblast influence on normal mouse mammary epithelial cell responses to estrogen in vitro. Cancer Res 45: 310–316

    Google Scholar 

  • Hoshino K (1964) Regeneration and growth of quantitatively transplanted mammary glands of normal female mice. Anat Rec 150: 221–236

    Google Scholar 

  • Jamieson S, Paterson FC, Monaghan P, Davies AC, Warburton MJ (1986) Isolation and properties of rat cell lines morphologically intermediate between cultured mammary epithelial and myoepithelial cells. Dev Biol 113: 388–405

    Google Scholar 

  • Korfsmeier K-H (1979) Proliferation kinetics in the mammary gland of the mouse during postnatal development. Anat Anz 145: 313–318

    Google Scholar 

  • Kratochwil K (1977) Development and loss of androgen responsiveness in the embryonic rudement of the mouse mammary gland. Dev Biol 61: 358–365

    Google Scholar 

  • — (1987) Epithelium—mesenchyme interaction in the fetal mammary gland. In: Medina D, Kidwell W, Heppner G, Anderson E (eds) Cellular and molecular biology of mammary cancer. Plenum, New York, pp 67–80

    Google Scholar 

  • Medina D (1979) Serial transplantation of chemical carcinogen-induced mouse mammary ductal dysplasias. J Natl Cancer Inst 62: 397–405

    Google Scholar 

  • — (1988) The preneoplastic state in mouse mammary tumorigenesis. Carcinogenesis 9: 1113–1119

    Google Scholar 

  • —, Kittrell FS (1987) Enhancement of tumorigenicity with morphological progression in a BALB/c preneoplastic outgrowth line. J Natl Cancer Inst 79: 569–576

    Google Scholar 

  • —, Oborn CJ, Kittrell FS, Ullrich RL (1986) Properties of mouse mammary epithelial cell lines characterized by in vivo transplantation and in vitro immunocytochemical methods. J Natl Cancer Inst 76: 1143–1156

    Google Scholar 

  • Ormerod EJ, Rudland (1985) Isolation and characterization of cloned epithelial cell lines from normal rat mammary glands. In Vitro 21: 143–153

    Google Scholar 

  • Paterson FC, Rudland PS (1985) Identification of novel stage-specific polypeptides associated with the differentiation of mammary epithelial stem cells to alveolar-like cells in culture. J Cell Physiol 124: 525–538

    Google Scholar 

  • Silberstein GB, Daniel CW (1982) Elvax 40P implants, sustained local release of bioactive molecules influencing mammary ductal development. Dev Biol 93: 272–278

    Google Scholar 

  • —, Strickland P, Trumpbour V, Coleman S, Daniel CW (1984) In vivo, cAMP stimulates growth and morphogenesis of mouse mammary ducts. Proc Natl Acad Sci USA 81: 4950–4954

    Google Scholar 

  • —, Coleman S, Daniel CW (1990) Epithelium-dependent extracellular matrix synthesis in transforming growth factor Blgrowth-inhibited mouse mammary gland. J Cell Biol 110: 2209–2219

    Google Scholar 

  • Smith GH, Medina D (1988) A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland. J Cell Sci 89: 173–183

    Google Scholar 

  • —, Mehrel T, Roop DR (1990) Differential keratin gene expression in developing, differentiating, preneoplastic, and neoplastic mouse mammary epithelium. Cell Growth Differ 1: 161–170

    Google Scholar 

  • Sonnenberg A, Daams H, VanderValk MA, Hilkens J, Hilgers J (1986) Development of mouse mammary gland: identification of stages in differentiation of luminal and myoepithelial cells using monoclonal antibodies and polyvalent antiserium against keratin. J Histochem Cytochem 34: 1037–1043

    Google Scholar 

  • Vonderhaar BK (1987) Local effect of EGF, α-TGF and EGF-like growth factors on lobuloalveolar development of the mouse mammary gland in vivo. J Cell Physiol 132: 581–584

    Google Scholar 

  • Williams JM, Daniel CW (1983) Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol 97: 274–290

    Google Scholar 

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Dedicated to Professor Stuart Patton on the occassion of his 70th birthday.

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Medina, D., Smith, G.H. In search of mammary gland stem cells. Protoplasma 159, 77–84 (1990). https://doi.org/10.1007/BF01322591

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  • DOI: https://doi.org/10.1007/BF01322591

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