Journal of Mammary Gland Biology and Neoplasia

, Volume 1, Issue 1, pp 21–35

Role of mesenchymal-epithelial interactions in mammary gland development

  • Gerald R. Cunha
  • Yun Kit Hom
Article

Abstract

The mammary gland is a hormone-target organ derived from epidermis and develops as a result of reciprocal mesenchymal-epithelial interactions. The induction of mammary differentiation from indifferent epidermal cells by mammary mesenchyme implies induction of the complement of hormone receptors characteristic of normal mammary epithelium in cells of the epidermis. Considering the facts that mammary epithelial differentiation is induced by mammary mesenchyme and that certain aspects of hormone response (androgen-induced mammary regression) are inextricably linked to mesenchymal-epithelial interactions, it is evident that the biology of the mammary gland arises from and is maintained via cell-cell interactions. As a corollary, perturbation of stromal-epithelial interactions in adulthood may play a role in mammary carcinogenesis and in turn may provide opportunities for differentiation therapy.

Key words

Mesenchymal-epithelial interactions stromal-epithelial interactions mammary mesenchyme androgen receptors Wnt-1 keratinocyte growth factor mammary gland development ductal morphogenesis end buds mammary fat pad 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    C. C. Boring, T. S. Squires, and T. Tong (1992). Cancer statistics, 1992.Ca Cancer J. Clin. 4219–38.PubMedGoogle Scholar
  2. 2.
    G. R. Cunha, A. A. Donjacour, P. S. Cooke, S. Mee, R. M. Bigsby, S. J. Higgins, and Y. Sugimura (1987). The endocrinology and developmental biology of the prostate.Endocrine Rev. 8338–363.Google Scholar
  3. 3.
    T. Sakakura (1991). New aspects of stroma-parenchyma relations in mammary gland differentiation.Int. Rev. Cytol. 125165–202.PubMedGoogle Scholar
  4. 4.
    K. Haffen, M. Kedinger, and P. Simon-Assmann (1987). Mesenchyme-dependent differentiation of epithelial progenitor cells in the gut.J. Pediatr. Gastroenterol. Nutr. 614–23.PubMedGoogle Scholar
  5. 5.
    T. Sakakura (1987). Mammary embryogensis. In C. W. Neville and M. C. Daniel (eds.),The Mammary Gland: Development, Regulation, and Function Plenum Press, New York, pp. 37–66.Google Scholar
  6. 6.
    K. Kratochwil (1987). Tissue combination and organ culture studies in the development of the embryonic mammary gland. In R. B. L. Gwatkin (ed.),Developmental Biology: A Comprehensive Synthesis Plenum Press, New York, pp. 315–334.Google Scholar
  7. 7.
    C. W. Daniel and G. B. Silberstein (1987). Postnatal development of the rodent mammary gland. In M. C. Neville and C. W. Daniel (eds.),The Mammary Gland Development, Regulation and Function Plenum Press, New York, pp. 3–36.Google Scholar
  8. 8.
    A. Raynaud (1961). Morphogenesis of the mammary gland. In S. K. Kon and A. T. Cowie (eds.),Milk: The Mammary Gland and Its Secretion Academic Press, New York, pp. 3–46.Google Scholar
  9. 9.
    A. Propper (1972). Rôle du mésenchyme dans la différenciation de la glande mammaire chez l'embryon de lapin.Bull. Soc. Zool. Fr. 97505–512.Google Scholar
  10. 10.
    B. I. Balinsky (1950). On the developmental processes in mammary glands and other epidermal structures.Trans. R. Soc. Edinb. 621–31.Google Scholar
  11. 11.
    A. Y. Propper (1978). Wandering epithelial cells in rabbit embryo milk line.Dev. Biol. 67225–231.CrossRefPubMedGoogle Scholar
  12. 12.
    G. R. Cunha, P. Young, K. Christov, R. Guzman, S. Nandi, F. Talamantes, and G. Thordarson (1995). Mammary phenotypic expression induced in epidermal cells by embryonic mammary mesenchyme.Acta Anat. 152195–204.PubMedGoogle Scholar
  13. 13.
    J. Taylor-Papadimitriou and E. B. Lane (1987). Keratin expression in the mammary gland. In M. C. Neville and C. W. Daniel (eds.),The Mammary Gland: Development, Regulation, and Function Plenum Press, New York, pp. 181–215.Google Scholar
  14. 14.
    T. Sakakura, Y. Nishizuka, and C. J. Dawe (1976). Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland.Science 1941439–1441.PubMedGoogle Scholar
  15. 15.
    G. R. Cunha, P. Young, S. Hamamoto, R. Guzman, and S. Nandi (1992). Developmental response of adult mammary epithelial cells to various fetal and neonatal mesenchymes.Epithelial Cell Biol. 1105–118.PubMedGoogle Scholar
  16. 16.
    K. Kratochwil (1975). Experimental analysis of the prenatal development of the mammary gland.Mod. Probl. Pediat. 151–15.Google Scholar
  17. 17.
    R. Nusse and H. E. Varmus (1992). Wnt genes.Cell 691073–1087.CrossRefPubMedGoogle Scholar
  18. 18.
    K. Kratochwil and P. Schwartz (1976). Tissue interaction in androgen response of embryonic mammary rudiment of mouse: Identification of target tissue of testosterone.Proc. Natl. Acad. Sci. USA 734041–4044.PubMedGoogle Scholar
  19. 19.
    K. Korach (1994). Insights from the study of animals lacking functional estrogen receptor.Science 2661524–1527.PubMedGoogle Scholar
  20. 20.
    Y. Matsui, S. A. Halter, J. T. Holt, B. L. M. Hogan, and R. J. Coffey (1990). Development of mammary hyperplasia and neoplasia in MMTV-TGFα transgenic mice.Cell 611147–1155.CrossRefPubMedGoogle Scholar
  21. 21.
    C. Jhappan, C. Stahle, R. N. Harkins, N. Fausto, G. H. Smith, and G. T. Merlino (1990). TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.Cell 611137–1146.CrossRefPubMedGoogle Scholar
  22. 22.
    E. P. Sandgren, N. C. Luetteke, R. D. Palmiter, R. L. Brinster, and D. C. Lee (1990). Overexpression of TGFα in transgenic mice: Induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast.Cell 611121–1135.CrossRefPubMedGoogle Scholar
  23. 23.
    G. Stamp, V. Fantl, R. Poulsom, S. Jamieson, R. Smith, G. Peters, and C. Dickson (1992). Nonuniform expression of a mouse mammary tumor virus-drivenint-2/Fgf-3 transgene in pregnancy-responsive breast tumors.Cell Growth Differ. 3929–938.PubMedGoogle Scholar
  24. 24.
    J. W. Muller, F. S. Lee, C. Dickson, G. Peters, P. Pattengale, and P. Leder (1990). Theint-2 gene product acts as an epithelial growth factor in transgenic mice.EMBO J. 9907–913.PubMedGoogle Scholar
  25. 25.
    A. S. Tsukamoto, R. Grosschedl, R. C. Guzman, T. Parslow, and H. E. Varmus (1988). Expression of theint-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice.Cell 59619–625.CrossRefGoogle Scholar
  26. 26.
    D. F. Pierce, Jr., M. D. Johnson, Y. Matsui, S. D. Robinson, L. I. Gold, A. F. Purchio, C. W. Daniel, B. L. Hogan, and H. L. Moses (1993). Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1.Genes Dev. 72308–2317.PubMedGoogle Scholar
  27. 27.
    T. P. Lin, R. C. Guzman, R. C. Osborn, G. Thordarson, and S. Nandi (1992). Role of endocrine, autocrine, and paracrine interactions in the development of mammary hyperplasia in Wnt-1 transgenic mice.Cancer Res. 524413–4419.PubMedGoogle Scholar
  28. 28.
    K. Kratochwil (1977). Development and loss of androgen responsiveness in the embryonic rudiment of the mouse mammary gland.Dev. Biol. 61358–365.CrossRefPubMedGoogle Scholar
  29. 29.
    T. Sakakura, Y. Sakagami, and Y. Nishizuka (1982). Dual origin of mesenchymal tissues participating in mouse mammary gland embryogenesis.Dev. Biol. 91202–207.CrossRefPubMedGoogle Scholar
  30. 30.
    K. B. DeOme, L. J. Faulkin, Jr., and H. A. Bern (1959). Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice.Cancer Res. 19515–520.PubMedGoogle Scholar
  31. 31.
    T. Sakakura, I. Kusano, M. Kusakabe, Y. Inaguma, and Y. Nishizuka (1987). Biology of mammary fat pad in fetal mouse: Capacity to support development of various fetal epitheliain vivo.Development 100421–430.PubMedGoogle Scholar
  32. 32.
    R. Narbaitz, W. E. Stumpf, and M. Sar (1980). Estrogen receptors in mammary gland primordia of fetal mouse.Anat. Embryol. 158161–166.CrossRefPubMedGoogle Scholar
  33. 33.
    S. Z. Haslam and G. Shyamala (1981). Relative distribution of estrogen and progesterone receptors among the epithelial, adipose, and connective tissue components of the normal mammary gland.Endocrinology 108825–830.PubMedGoogle Scholar
  34. 34.
    M. J. Bissell and H. G. Hall (1987). Form and function in the mammary gland: The role of extracellular matrix. In M. C. Neville and C. W. Daniel (eds.),The Mammary Gland: Development, Regulation, and Function Plenum Press, New York, pp. 97–146.Google Scholar
  35. 35.
    S. Nandi (1958). Endocrine control of mammary gland development and function in the C3H/He Crgl mouse.J. Natl. Cancer Inst. 211039–1063.PubMedGoogle Scholar
  36. 36.
    R. L. Ceriani (1970). Fetal mammary gland differentiationin vitro in response to hormones. I. Morphological findings.Dev. Biol. 21506–529.CrossRefPubMedGoogle Scholar
  37. 37.
    R. L. Ceriani (1970). Fetal mammary gland differentiationin vitro in response to hormones. II. Biochemical findings.Dev. Biol. 21530–546.CrossRefPubMedGoogle Scholar
  38. 38.
    H. Nagasawa and T. Mori (1988). Long-term effects of perinatal exposure to hormones and related substances on normal and neoplastic growth of murine mammary glands. In T. Mori and H. Nagasawa (eds.),Toxicity of Hormones in Perinatal Life CRC Press, Boca Raton, Florida pp. 81–88.Google Scholar
  39. 39.
    S. Z. Haslam and K. A. Nummy (1992). The ontogeny and cellular distribution of estrogen receptors in normal mouse mammary gland.J. Steroid Biochem. Mol. Biol. 42589–595.CrossRefPubMedGoogle Scholar
  40. 40.
    B. Mintz (1978). Genetic mosaicism andin vivo analyses of neoplasia and differentiation. In G. Saunders (ed.),Cell Differentiation and Neoplasia Raven Press, New York, pp. 27–56.Google Scholar
  41. 41.
    G. R. Cunha, N. Hayashi, and Y. C. Wong (1991). Regulation and growth of normal adult and neoplastic epithelial by inductive mesenchyme. In J. T. Issacs (ed.),Prostate Cancer: Cell and Molecular Mechanisms in Diagnosis and Treatment Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, pp. 73–90.Google Scholar
  42. 42.
    J. J. De Cosse, C. L. Gossens, J. F. Kuzma, and B. R. Unsworth (1975). Embryonic inductive tissues that cause histological differentiation of murine mammary carcinomain vitro.J. Natl. Cancer Inst. 54913–921.PubMedGoogle Scholar
  43. 43.
    S. Sakaguchi, T. Takahashi, T. Sakakura, Y. Sakagami, Y. Nishizuka, and H. Tanaka (1981). Earlier appearance of murine mammary tumor virus-associated antigens in duct-alveolus nodules induced by transplantation of fetal salivary mesenchyme into C3H mouse mammary glands.Gann 72982–987.PubMedGoogle Scholar
  44. 44.
    T. Sakakura (1983). Epithelial-mesenchymal interactions in mammary gland development and its perturbation in relation to tumorigenesis. In M. A. Rich, J. C. Hager, and P. Furmanski (eds.),Understanding Breast Cancer: Clinical and Laboratory Concepts Marcel Dekker, New York, pp. 261–284.Google Scholar
  45. 45.
    T. Sakakura, Y. Sakagami, and Y. Nishizuka (1981). Accelerated mammary cancer development by fetal salivary mesenchyme isografted to adult mouse mammary epithelium.J. Natl. Cancer Inst. 66953–959.PubMedGoogle Scholar
  46. 46.
    G. B. Silberstein and C. W. Daniel (1987). Reversible inhibition of mammary gland growth by transforming growth factor-beta.Science 237291–293.PubMedGoogle Scholar
  47. 47.
    C. W. Daniel and S. D. Robinson (1992). Regulation of mammary growth and function by TGF-beta.Mol. Reprod. Dev. 32145–151.CrossRefPubMedGoogle Scholar
  48. 48.
    S. P. Ethier and R. M. Van de Velde (1990). Secretion of a TGF-β-like growth inhibitor by normal rat mammary epithelial cellsin vitro.J. Cell. Physiol. 14215–20.CrossRefPubMedGoogle Scholar
  49. 49.
    C. Knabbe, M. E. Lippman, L. M. Wakefield, K. C. Flanders, A. Kasid, R. Derynck, and R. B. Dickson (1987). Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells.Cell 48417–428.CrossRefPubMedGoogle Scholar
  50. 50.
    C. W. Daniel, G. B. Silberstein, K. Van Horn, P. Strickland, and S. Robinson (1989). TGF-β1-Induced inhibition of mouse mammary ductal growth: Developmental specificity and characterization.Dev. Biol. 13520–30.CrossRefPubMedGoogle Scholar
  51. 51.
    S. D. Robinson, G. B. Silberstein, A. B. Roberts, K. C. Flanders, and C. W. Daniel (1991). Regulated expression and growth inhibitory effects of transforming growth factor-β isoforms in mouse mammary gland development.Development 113867–878.PubMedGoogle Scholar
  52. 52.
    G. B. Silberstein, S. Strickland, S. Coleman, and C. W. Daniel (1990). Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland.J. Cell Biol. 1102209–2219.PubMedGoogle Scholar
  53. 53.
    G. B. Silberstein, K. C. Flanders, A. B. Roberts, and C. W. Daniel (1992). Regulation of mammary morphogenesis: Evidence for extracellular matrix-mediated inhibition of ductal budding by transforming growth factor-beta 1.Dev. Biol. 152354–362.CrossRefPubMedGoogle Scholar
  54. 54.
    S. D. Robinson, A. B. Roberts, and C. W. Daniel (1993). TGF beta suppresses casein synthesis in mouse mammary explants and may play a role in controlling milk levels during pregnancy.J. Cell Biol. 120245–251.PubMedGoogle Scholar
  55. 55.
    A. W. Sudlow, C. J. Wilde, and R. D. Burgoyne (1994). Transforming growth factor-beta 1 inhibits casein secretion from differentiating mammary-gland explants but not from lactating mammary cells.Biochem J. 304333–336.PubMedGoogle Scholar
  56. 56.
    T. Yamamoto, H. Komura, K. Morishige, C. Tadokoro, M. Sakata, H. Kurachi, and A. Miyake (1994). Involvement of autocrine mechanism of transforming growth factor-beta in the functional differentiation of pregnant mouse mammary gland.Eur. J. Endocrinol. 130302–307.PubMedGoogle Scholar
  57. 57.
    M. Mieth, F. D. Boehmer, R. Ball, B. Groner, and R. Grosse (1990). Transforming growth factor-beta inhibits lactogenic hormone induction of beta-casein expression in HC11 mouse mammary epithelial cells.Growth Factors 49–15.PubMedGoogle Scholar
  58. 58.
    C. Jhappan, A. G. Geiser, E. C. Kordon, D. Bagheri, L. Hennighausen, A. B. Roberts, G. H. Smith, and G. Merlino (1993). Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation.EMBO J. 121835–1845.PubMedGoogle Scholar
  59. 59.
    D. S. Liscia, G. Merlo, F. Ciardiello, N. Kim, G. H. Smith, R. Callahan, and D. S. Salomon (1990). Transforming growth factor-alpha messenger RNA localization in the developing adult rat and human mammary gland byin situ hybridization.Dev. Biol. 140123–131.CrossRefPubMedGoogle Scholar
  60. 60.
    S. M. Snedeker, C. F. Brown, and R. P. DiAugustine (1991). Expression and functional properties of transforming growth factor α and epidermal growth factor during mouse mammary gland ductal morphogenesis.Proc. Natl. Acad. Sci. USA 88276–280.PubMedGoogle Scholar
  61. 61.
    E. M. Valverius, S. E. Bates, M. R. Stampfer, R. Clark, F. McCormick, D. S. Salomon, M. E. Lippman, and R. B. Dickson (1989). Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells.Mol. Endocrinol 3203–214.PubMedGoogle Scholar
  62. 62.
    W. Imagawa, G. K. Bandyopadhyay, and S. Nandi (1990). Regulation of mammary epithelial cell growth in mice and rats.Endocrine Rev. 11494–523.Google Scholar
  63. 63.
    B. K. Vonderhaar (1987). Local effects of EGF, alpha-TGF, and EGF-like growth factors on lobuloalveolar development of the mouse mammary glandin vivo.J. Cell. Physiol. 132581–584.CrossRefPubMedGoogle Scholar
  64. 64.
    R. J. Coffey, Jr., K. S. Meise, Y. Matsui, B. L. Hogan, P. J. Dempsey, and S. A. Halter (1994). Acceleration of mammary neoplasia in transforming growth factor alpha transgenic mice by 7,12-dimethylbenzanthracene.Cancer Res. 541678–1683.PubMedGoogle Scholar
  65. 65.
    S. A. Halter, P. Dempsey, Y. Matsui, M. K. Stokes, D. R. Graves, B. L. Hogan, and R. J. Coffey (1992). Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations.Am. J. Pathol. 1401131–1146.PubMedGoogle Scholar
  66. 66.
    S. Sakai, M. Mizuno, T. Harigaya, K. Yamamoto, T. Mori, R. J. Coffey, and H. Nagasawa (1994). Cause of failure of lactation in mouse mammary tumor virus/human transforming growth factor alpha transgenic mice.Proc. Soc. Exp. Biol. Med. 205236–242.PubMedGoogle Scholar
  67. 67.
    S. A. Aaronson, J. S. Rubin, P. W. Finch, J. Wong, C. Marchese, J. Falco, W. G. Taylor, and M. H. Kraus (1990). Growth factor-regulated pathways in epithelial cell proliferation.Am. Rev. Respir. Dis. 142S7–10.PubMedGoogle Scholar
  68. 68.
    W. Imagawa, G. R. Cunha, P. Young, and S. Nandi (1994). Keratinocyte growth factor and acidic fibroblast growth factor are mitogens for primary cultures of mammary epithelium.Biochem. Biophys. Res. Commun. 2041165–1169.CrossRefPubMedGoogle Scholar
  69. 69.
    T. R. Ulich, E. S. Yi, R. Cardiff, S. Yin, N. Bikhazi, R. Biltz, C. F. Morris, and G. F. Pierce (1994). Keratinocyte growth factor is a growth factor for mammary epitheliumin vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.Am. J. Pathol. 144862–868.PubMedGoogle Scholar
  70. 70.
    E. S. Yi, A. A. Bedoya, H. Lee, S. Kim, R. M. Housley, S. L. Aukerman, J. E. Tarpley, C. Starnes, C. Starnes, S. Yin, G. F. Pierce,et al. (1994). Keratinocyte growth factor causes cystic dilation of the mammary glands of mice. Interactions of keratinocyte growth factor, estrogen, and progesteronein vivo.Am. J. Pathol. 1451015–1022.PubMedGoogle Scholar
  71. 71.
    T. R. Ulich, E. S. Yi, K. Longmuir, S. Yin, R. Biltz, C. F. Morris, R. M. Housley, and G. F. Pierce (1994). Keratinocyte growth factor is a growth factor for type II pneumocytesin vivo.J. Clin. Invest. 931298–1306.PubMedGoogle Scholar
  72. 72.
    P. W. Finch, G. R. Cunha, J. S. Rubin, J. Wong, and D. Ron (1995). Pattern of KGF and KGFR expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions.Dev. Dynam. (in press).Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Gerald R. Cunha
    • 1
  • Yun Kit Hom
    • 1
  1. 1.Anatomy Department and Reproductive Endocrinology CenterUniversity of CaliforniaSan Francisco

Personalised recommendations