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J Cell Biol. Apr 1, 1990; 110(4): 1405–1415.
PMCID: PMC2116068

Expression of extracellular matrix components is regulated by substratum

Abstract

Reconstituted basement membranes and extracellular matrices have been demonstrated to affect, positively and dramatically, the production of milk proteins in cultured mammary epithelial cells. Here we show that both the expression and the deposition of extracellular matrix components themselves are regulated by substratum. The steady-state levels of the laminin, type IV collagen, and fibronectin mRNAs in mammary epithelial cells cultured on plastic dishes and on type I collagen gels have been examined, as has the ability of these cells to synthesize, secrete, and deposit laminin and other, extracellular matrix proteins. We demonstrate de novo synthesis of a basement membrane by cells cultured on type I collagen gels which have been floated into the medium. Expression of the mRNA and proteins of basement membranes, however, are quite low in these cultures. In contrast, the levels of laminin, type IV collagen, and fibronectin mRNAs are highest in cells cultured on plastic surfaces, where no basement membrane is deposited. It is suggested that the interaction between epithelial cells and both basement membrane and stromally derived matrices exerts a negative influence on the expression of mRNA for extracellular matrix components. In addition, we show that the capacity for lactational differentiation correlates with conditions that favor the deposition of a continuous basement membrane, and argue that the interaction between specialized epithelial cells and stroma enables them to create their own microenvironment for accurate signal transduction and phenotypic function.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barcellos-Hoff MH, Aggeler J, Ram TG, Bissell MJ. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development. 1989 Feb;105(2):223–235. [PMC free article] [PubMed]
  • Barlow DP, Green NM, Kurkinen M, Hogan BL. Sequencing of laminin B chain cDNAs reveals C-terminal regions of coiled-coil alpha-helix. EMBO J. 1984 Oct;3(10):2355–2362. [PMC free article] [PubMed]
  • Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression? J Theor Biol. 1982 Nov 7;99(1):31–68. [PubMed]
  • Bissell DM, Arenson DM, Maher JJ, Roll FJ. Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver. J Clin Invest. 1987 Mar;79(3):801–812. [PMC free article] [PubMed]
  • Blum JL, Wicha MS. Role of the cytoskeleton in laminin induced mammary gene expression. J Cell Physiol. 1988 Apr;135(1):13–22. [PubMed]
  • Blum JL, Zeigler ME, Wicha MS. Regulation of rat mammary gene expression by extracellular matrix components. Exp Cell Res. 1987 Dec;173(2):322–340. [PubMed]
  • Bonner WM. Autoradiograms: 35S and 32P. Methods Enzymol. 1987;152:55–61. [PubMed]
  • Burwen SJ, Pitelka DR. Secretory function of lactating mouse mammary epithelial cells cultured on collagen gels. Exp Cell Res. 1980 Apr;126(2):249–262. [PubMed]
  • Caplan MJ, Stow JL, Newman AP, Madri J, Anderson HC, Farquhar MG, Palade GE, Jamieson JD. Dependence on pH of polarized sorting of secreted proteins. Nature. 1987 Oct 15;329(6140):632–635. [PubMed]
  • Carey DJ, Todd MS, Rafferty CM. Schwann cell myelination: induction by exogenous basement membrane-like extracellular matrix. J Cell Biol. 1986 Jun;102(6):2254–2263. [PMC free article] [PubMed]
  • Chen LH, Bissell MJ. Transferrin mRNA level in the mouse mammary gland is regulated by pregnancy and extracellular matrix. J Biol Chem. 1987 Dec 25;262(36):17247–17250. [PubMed]
  • Chen LH, Bissell MJ. A novel regulatory mechanism for whey acidic protein gene expression. Cell Regul. 1989 Nov;1(1):45–54. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • David G, Bernfield M. Type I collagen reduces the degradation of basal lamina proteoglycan by mammary epithelial cells. J Cell Biol. 1981 Oct;91(1):281–286. [PMC free article] [PubMed]
  • David G, Nusgens B, van der Schueren B, van Cauwenberge D, van den Berghe H, Lapière C. Collagen metabolism and basement membrane formation in cultures of mouse mammary epithelial cells. Induction of 'assembly' on fibrillar type I collagen substrata. Exp Cell Res. 1987 Jun;170(2):402–416. [PubMed]
  • Eisenstein RS, Rosen JM. Both cell substratum regulation and hormonal regulation of milk protein gene expression are exerted primarily at the posttranscriptional level. Mol Cell Biol. 1988 Aug;8(8):3183–3190. [PMC free article] [PubMed]
  • Emerman JT, Pitelka DR. Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro. 1977 May;13(5):316–328. [PubMed]
  • Emerman JT, Enami J, Pitelka DR, Nandi S. Hormonal effects on intracellular and secreted casein in cultures of mouse mammary epithelial cells on floating collagen membranes. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4466–4470. [PMC free article] [PubMed]
  • Feinberg AP, Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. [PubMed]
  • Glasser SR, Julian J, Decker GL, Tang JP, Carson DD. Development of morphological and functional polarity in primary cultures of immature rat uterine epithelial cells. J Cell Biol. 1988 Dec;107(6 Pt 1):2409–2423. [PMC free article] [PubMed]
  • Grant DS, Leblond CP, Kleinman HK, Inoue S, Hassell JR. The incubation of laminin, collagen IV, and heparan sulfate proteoglycan at 35 degrees C yields basement membrane-like structures. J Cell Biol. 1989 Apr;108(4):1567–1574. [PMC free article] [PubMed]
  • Hadley MA, Byers SW, Suárez-Quian CA, Kleinman HK, Dym M. Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vitro. J Cell Biol. 1985 Oct;101(4):1511–1522. [PMC free article] [PubMed]
  • Hadley MA, Byers SW, Suárez-Quian CA, Djakiew D, Dym M. In vitro models of differentiated Sertoli cell structure and function. In Vitro Cell Dev Biol. 1988 Jun;24(6):550–557. [PubMed]
  • Haeuptle MT, Suard YL, Bogenmann E, Reggio H, Racine L, Kraehenbuhl JP. Effect of cell shape change on the function and differentiation of rabbit mammary cells in culture. J Cell Biol. 1983 May;96(5):1425–1434. [PMC free article] [PubMed]
  • Hedin U, Bottger BA, Forsberg E, Johansson S, Thyberg J. Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells. J Cell Biol. 1988 Jul;107(1):307–319. [PMC free article] [PubMed]
  • Ignotz RA, Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed]
  • Ingber DE, Folkman J. How does extracellular matrix control capillary morphogenesis? Cell. 1989 Sep 8;58(5):803–805. [PubMed]
  • Kimata K, Sakakura T, Inaguma Y, Kato M, Nishizuka Y. Participation of two different mesenchymes in the developing mouse mammary gland: synthesis of basement membrane components by fat pad precursor cells. J Embryol Exp Morphol. 1985 Oct;89:243–257. [PubMed]
  • Kleinman HK, McGarvey ML, Hassell JR, Martin GR. Formation of a supramolecular complex is involved in the reconstitution of basement membrane components. Biochemistry. 1983 Oct 11;22(21):4969–4974. [PubMed]
  • Kubota Y, Kleinman HK, Martin GR, Lawley TJ. Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J Cell Biol. 1988 Oct;107(4):1589–1598. [PMC free article] [PubMed]
  • Kurkinen M, Barlow DP, Helfman DM, Williams JG, Hogan BL. Isolation of cDNA clones for basal lamina components: type IV procollagen. Nucleic Acids Res. 1983 Sep 24;11(18):6199–6209. [PMC free article] [PubMed]
  • Lane EB. Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization. J Cell Biol. 1982 Mar;92(3):665–673. [PMC free article] [PubMed]
  • Lee EY, Parry G, Bissell MJ. Modulation of secreted proteins of mouse mammary epithelial cells by the collagenous substrata. J Cell Biol. 1984 Jan;98(1):146–155. [PMC free article] [PubMed]
  • Lee EY, Lee WH, Kaetzel CS, Parry G, Bissell MJ. Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1419–1423. [PMC free article] [PubMed]
  • Li ML, Aggeler J, Farson DA, Hatier C, Hassell J, Bissell MJ. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc Natl Acad Sci U S A. 1987 Jan;84(1):136–140. [PMC free article] [PubMed]
  • Madri JA, Pratt BM, Tucker AM. Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix. J Cell Biol. 1988 Apr;106(4):1375–1384. [PMC free article] [PubMed]
  • Nickerson SC, Akers RM. Biochemical and ultrastructural aspects of milk synthesis and secretion. Int J Biochem. 1984;16(8):855–865. [PubMed]
  • Parry G, Lee EY, Farson D, Koval M, Bissell MJ. Collagenous substrata regulate the nature and distribution of glycosaminoglycans produced by differentiated cultures of mouse mammary epithelial cells. Exp Cell Res. 1985 Feb;156(2):487–499. [PubMed]
  • Parry G, Cullen B, Kaetzel CS, Kramer R, Moss L. Regulation of differentiation and polarized secretion in mammary epithelial cells maintained in culture: extracellular matrix and membrane polarity influences. J Cell Biol. 1987 Nov;105(5):2043–2051. [PMC free article] [PubMed]
  • Peters BP, Hartle RJ, Krzesicki RF, Kroll TG, Perini F, Balun JE, Goldstein IJ, Ruddon RW. The biosynthesis, processing, and secretion of laminin by human choriocarcinoma cells. J Biol Chem. 1985 Nov 25;260(27):14732–14742. [PubMed]
  • Reichmann E, Ball R, Groner B, Friis RR. New mammary epithelial and fibroblastic cell clones in coculture form structures competent to differentiate functionally. J Cell Biol. 1989 Mar;108(3):1127–1138. [PMC free article] [PubMed]
  • Rodriguez-Boulan E, Nelson WJ. Morphogenesis of the polarized epithelial cell phenotype. Science. 1989 Aug 18;245(4919):718–725. [PubMed]
  • Schuetz EG, Li D, Omiecinski CJ, Muller-Eberhard U, Kleinman HK, Elswick B, Guzelian PS. Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. J Cell Physiol. 1988 Mar;134(3):309–323. [PubMed]
  • Schwarzbauer JE, Tamkun JW, Lemischka IR, Hynes RO. Three different fibronectin mRNAs arise by alternative splicing within the coding region. Cell. 1983 Dec;35(2 Pt 1):421–431. [PubMed]
  • Servely JL, Geuens GM, Martel P, Houdebine LM, de Brabander M. Effect of tubulozole, a new synthetic microtubule inhibitor, on the induction of casein gene expression by prolactin. Biol Cell. 1987;59(2):121–127. [PubMed]
  • Shannon JM, Pitelka DR. The influence of cell shape on the induction of functional differentiation in mouse mammary cells in vitro. In Vitro. 1981 Nov;17(11):1016–1028. [PubMed]
  • Shannon JM, Mason RJ, Jennings SD. Functional differentiation of alveolar type II epithelial cells in vitro: effects of cell shape, cell-matrix interactions and cell-cell interactions. Biochim Biophys Acta. 1987 Nov 12;931(2):143–156. [PubMed]
  • Sugrue SP, Hay ED. The identification of extracellular matrix (ECM) binding sites on the basal surface of embryonic corneal epithelium and the effect of ECM binding on epithelial collagen production. J Cell Biol. 1986 May;102(5):1907–1916. [PMC free article] [PubMed]
  • Unemori EN, Bouhana KS, Werb Z. Vectorial secretion of extracellular matrix proteins, matrix-degrading proteinases, and tissue inhibitor of metalloproteinases by endothelial cells. J Biol Chem. 1990 Jan 5;265(1):445–451. [PubMed]
  • Warburton MJ, Kimbell R, Rudland PS, Ferns SA, Barraclough R. Control of type IV collagen production in rat mammary epithelial and myoepithelial-like cells. J Cell Physiol. 1986 Jul;128(1):76–84. [PubMed]
  • Wiens D, Park CS, Stockdale FE. Milk protein expression and ductal morphogenesis in the mammary gland in vitro: hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction. Dev Biol. 1987 Mar;120(1):245–258. [PubMed]
  • Wrana JL, Maeno M, Hawrylyshyn B, Yao KL, Domenicucci C, Sodek J. Differential effects of transforming growth factor-beta on the synthesis of extracellular matrix proteins by normal fetal rat calvarial bone cell populations. J Cell Biol. 1988 Mar;106(3):915–924. [PMC free article] [PubMed]

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