Cell and Tissue Research

, Volume 268, Issue 1, pp 167–177

Changes in the extracellular matrix of the normal human breast during the menstrual cycle

  • J. E. Ferguson
  • A. M. Schor
  • A. Howell
  • M. W. J. Ferguson
Article

Summary

The normal human mammary gland undergoes a well defined sequence of histological changes in both epithelial and stromal compartments during the menstrual cycle. Studies in vitro have suggested that the extracellular matrix surrounding the individual cells plays a central role in modulating a wide variety of cellular events, including proliferation, differentiation and gene expression. We therefore investigated the distribution of a number of extracellular matrix molecules in the normal breast during the menstrual cycle. By use of indirect immunofluorescence, with specific antibodies, we demonstrated that laminin, heparan sulphate proteoglycan, type IV collagen, type V collagen, chondroitin sulphate and fibronectin undergo changes in distribution during the menstrual cycle, whereas collagen types I, III, VI and VII remain unchanged. These changes were most marked in the basement membrane, sub-basement membrane zone and delimiting layer of fibroblasts surrounding the ductules where basement membrane markers such as laminin, heparan sulphate proteoglycan, and type IV and V collagens appear greatly reduced during the mid-cycle period (days 8 to 22). These results suggest that some extracellular matrix molecules may act as medittors in the hormonal control of the mammary gland, whereas others may have a predominantly structural role.

Key words

Mammary gland Extracellular matrix Menstrual cycle Breast cancer Immunohistochemistry Epithelial cell behaviour Human 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bassols A, Massague J (1988) Transforming growth factor β regulates the expression and structure of extracellular matrix chondroitin;dermatan sulfate proteoglycans. J Biol Chem 262:3039–3045Google Scholar
  2. Briozzo P, Morisset M, Capany F, Rougeot C, Rochefort H (1988) In vivo degradation of extracellular matrix with Mr 52000 cathepsin-D secreted by breast cancer cells. Cancer Res 48:3688–3692Google Scholar
  3. Castronovo V, Taraboletti G, Liotta LA, Sobel ME (1989) Modulation of laminin receptor expression by estrogen and progestins in tumour breast cancer cell lines. J Natl Cancer Inst 81:781–789Google Scholar
  4. Emerman JT, Pitelka DR (1977) Maintenance and identification of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro Cell Dev Biol 13:316–328Google Scholar
  5. Fanger H, Ree HJ (1974) Cyclic changes of human mammary gland epithelium in relation to the menstrual cycle. An ultrastructural study. Cancer 34:574–585Google Scholar
  6. Ferguson DJP, Anderson TJ (1981) Morphological evaluation of cell turnover in relation to the menstrual cycle in the ‘resting’ human breast. Br J Cancer 44:177–181Google Scholar
  7. Ferguson JE, Schor AM, Howell A, Ferguson MWJ (1990) Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma. Differentiation 42:199–207Google Scholar
  8. Huff KK, Knabbe C, Lindsay R, Kaufman D, Bransent D, Lippman M, Dickson RB (1988) Multihormonal regulation of insulin like growth factor-1-related protein in MCF-7 human breast cancer cells. Mol Cell Endocrinol 2:200–208Google Scholar
  9. Ignotz RA, Massague J (1986) Transforming growth factor-β stimulates the expression of fibronectin and collagen and their incorporation into the exctracellular matrix. J Biol Chem 261:4337–4345Google Scholar
  10. Ignotz RA, Endo T, Massague J (1987) Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor β. J Biol Chem 262:6443–6446Google Scholar
  11. Johnston GD, Davidson RS, McNamee KC, Russell G, Goodwin D, Holborow EJ (1982) Fading of immunofluorescence during microscopy: a study of the phenomenon and its remedy. J Immunol Methods 55:231–242Google Scholar
  12. Kefalides NA, Alper R, Clark CC (1979) Biochemistry and metabolism of basement membranes. Int Rev Cytol 61:167–228Google Scholar
  13. Knabbe C, Lippman M, Wakefield LM, Fianders KC, Kasill A, Derynck R, Dickson RB (1987) Evidence that transforming growth factors β is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48:417–428Google Scholar
  14. Li ML, Aggeler J, Farson DA, Hatier C, Hassel J, Bissel MJ (1987) Influence of reconstituted basement membrane and its components on casein gene expression and secretion on mouse mammary epithelial cells. Proc Natl Acad Sci USA 84:136–140Google Scholar
  15. Liotta LA, Wicha MS, Foidart JM, Rennards I, Garbisa S, Kidwell WR (1979) Hormonal requirements for basement membrane collagen deposition by cultured rat mammary epithelium. Lab Invest 41:511–518Google Scholar
  16. Longacre TA, Bartow SA (1986) A correlative morphologic study of human breast and endometrium in the menstrual cycle. Am J Surg Pathol 10:382–393Google Scholar
  17. Mark HK von der, Gay S (1976) Study of differential collagen synthesis during the development of the chick embryo by immunofluorescence. I. The preparation of type I and II specific antibodies and their application to early stages of the chick embryo. Dev Biol 48:237–249Google Scholar
  18. Mark HK von der, Ocalan M (1982) Immunofluorescent localisation of type V collagen in the chick embryo with mouse monoclonal antibody. Coll Relat Res 2:541–555Google Scholar
  19. McGrath M, Palmer S, Nandi S (1985) Differential response of normal rat mammary epithelial cells to mammogenic hormones and EGF. J Cell Physiol 125:182–191Google Scholar
  20. Moscatelli D, Rifkin DB (1988) Membrane and matrix localisation of proteinases: a common theme in tumour cell invasion and angiogenesis. Biochim Biophys Acta 948:67–85Google Scholar
  21. Mukku VR, Stancel GM (1985) Regulation of epdermal growth factor receptor by estrogen. J Biol Chem 260:9820–9824Google Scholar
  22. Narayanan AS, Page RC (1983) Biosynthesis and regulation of type V collagen in diploid human fibroblasts. J Biol Chem 258:11694–11699Google Scholar
  23. Ozello L (1970) Epithelial-stromal junction of normal and dysplastic mammary glands. Cancer 23:586–600Google Scholar
  24. Ozello L, Speer FD (1958) The mucopolysaccharides in the normal and diseased breast. Their distribution and significance. Am J Pathol 34:993–1009Google Scholar
  25. Park CS, Bissel MJ (1988) Messenger RNA for basement membrane components in the mouse mammary gland and in cells in culture (abstract). J Cell Biol 103:388Google Scholar
  26. Parry G, Cullen B, Kaetzel CS, Kramer R, Moss L (1987) Regulation of differentiation and polarized secretion in mammary epithelial cells maintained in culture. Extracellular matrix and membrane polarity influences. J Cell Biol 105:2043–2051Google Scholar
  27. Pearson CA, Pearson D, Shibahara S, Hofsteenge J, Chiquet-Ehrisman R (1988) Tenascin: cDNA cloning and induction by TGF β. EMBO J:2977–2981Google Scholar
  28. Pollow K, Sinnecker R, Schmidt-Gollwitzer M, Boquio E, Pollow B (1977) Binding of progesterone to normal and neoplastic tissue samples from tumour bearing breast. J Mol Med 2:69–82Google Scholar
  29. Poole AR, Tiltman KJ, Recklies AD, Stoker TAM (1978) Differences in secretion of the proteinase cathepsin B at the edges of human breast carcinoma and fibroadenoma. Nature 273:545–547Google Scholar
  30. Potten CS, Watson RJ, Williams GT, Tickle S, Roberts SA, Harris M, Howell A (1988) The effect of age and menstrual cycle upon proliferative activity of the normal human breast. Br J Cancer 58:163–170Google Scholar
  31. Roberts CJ, Birkenmeier TM, McQuilla JJ, Akiyama SK, Yamada S, Chen WT, Yamada K, McDonald J (1988) Transforming growth factor β stimulates the expression of fibronectin and of both subunits of the human fibronectin receptor by cultured human lung fibroblasts. J Biol Chem 263:4586–4592Google Scholar
  32. Sakakura T, Nishizuka Y, Dawe CJ (1976) Mesenchyme dependent morphogenesis and epithelium specific cytodifferentiation in mouse mammary gland. Science 194:1439–1441Google Scholar
  33. Salomon DS, Liotta LA, Kidwell WR (1981) Differential response to growth factors by rat mammary epithelium plated on different collagen substrata in serum free medium. Proc Natl Acad Sci USA 78:382–386Google Scholar
  34. Shannon JM, Pitelka DR (1981) The influence of cell shape on the induction of functional differentiation in mouse mammary cells in vitro. In Vitro Cell Dev Biol 17:1016–1028Google Scholar
  35. Silva JS, Georgiade GS, Dilley WG, McCarty KS Sr, Wells SA, McCarty KS Jr (1983) Menstrual cycle-dependent variations of breast cyst fluid proteins and sex steroid receptors in the normal human breast. Cancer 51:1297–1302Google Scholar
  36. Suard YML, Haeuptle MT, Fannon E, Kraehenbuhl JP (1983) Cell proliferation and milk protein gene expression in rabbit mammary cell cultures. J Cell Biol 96:1435–1442Google Scholar
  37. Taketani Y, Mizuno M (1988) Cyclic changes in epidermal growth factor receptor in human endometrium during menstrual cycle. Endocrinol Jpn 35:19–25Google Scholar
  38. Talhouk RS, Chin JR, Unemori EN, Werb Z, Bissell MJ (1991) Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture. Development 112:439–449Google Scholar
  39. Varga J, Rosenbloom J, Jimenez S (1987) Transforming growth factor β (TGFβ) causes a persistent increase in steady state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. Biochem J 247:597–604Google Scholar
  40. Vlodavsky I, Fuks Z, Bar-Ner M, Yahalom J, Eldor A, Savion N, Naparstek Y, Cohen I, Kramer M, Schirrmacher V (1985) Degradation of heparan sulphate in the subendothelial basement membrane by normal and blood borne cells. In: May B (ed) Extracellular matrix; structure and function. Plenum, New York, pp 283–308Google Scholar
  41. Vogel PM, Georgiade NG, Fetter BF, Vogel FS, McCarty KS (1981) The correlation of histological changes in the human breast with the menstrual cycle. Am J Pathol 104:23–34Google Scholar
  42. Wicha MS, Liotta LA, Garbisa S, Kidwell WR (1979) Basement membrane collagen requirements for attachment and growth of mammary epithelium. Exp Cell Res 124:181–190Google Scholar
  43. Wicha MS, Liotta LA, Vonderhaar BK, Kidwell WR (1980) Effects of inhibition of basement membrane collagen deposition on rat mammary gland development. Dev Biol 80:253–266Google Scholar
  44. Williams JM, Daniel CW (1983) Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol 97:274–290Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • J. E. Ferguson
    • 1
  • A. M. Schor
    • 1
  • A. Howell
    • 1
  • M. W. J. Ferguson
    • 2
  1. 1.CRC Department of Medical Oncology and Holt Radium InstituteChristie HospitalManchesterUK
  2. 2.Department of Cell and Structural BiologyUniversity of ManchesterManchesterUK

Personalised recommendations