Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Aug 1982; 79(15): 4672–4676.
PMCID: PMC346738

Lumen formation by epithelial cell lines in response to collagen overlay: a morphogenetic model in culture.


Two cell lines--Madin-Darby canine kidney (MDCK) and normal murine mammary gland (NMuMG)--growing as monolayers on collagen gels were overlaid with another collagen gel. The cells responded to the overlay by undergoing reorganization resulting in the creation of lumina. MDCK cells formed lumina that coalesced to form large cavities comparable in size with a tubule. NMuMG cells formed clusters surrounding small lumina, which appeared similar to acini of glandular tissue. The characteristic arrangements, described here by light and electron microscopy, resembled the morphology of the tissues of cell line origin. MDCK cells, grown in the presence of serum, formed lumina whether or not serum was removed at the time of overlay, whereas NMuMG cells required either a nondialyzable component of serum or hormonal supplements in serum-free defined media. Lumen formation was delayed by MDCK cells in the presence of the glutamine analog 6-diazo-5-oxo-L-norleucine, but this compound did not affect NMuMG lumen formation. In both cell lines, lumen formation was unaffected by the absence of sulfate, the presence of an inhibitor of sulfated glycosaminoglycan synthesis, or an inhibitor of collagen synthesis. DNA synthesis accompanied lumen formation but was not required.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Liotta LA, Abe S, Robey PG, Martin GR. Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proc Natl Acad Sci U S A. 1979 May;76(5):2268–2272. [PMC free article] [PubMed]
  • Ingber DE, Madri JA, Jamieson JD. Role of basal lamina in neoplastic disorganization of tissue architecture. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3901–3905. [PMC free article] [PubMed]
  • Emerman JT, Burwen SJ, Pitelka DR. Substrate properties influencing ultrastructural differentiation of mammary epithelial cells in culture. Tissue Cell. 1979;11(1):109–119. [PubMed]
  • Taub M, Chuman L, Saier MH, Jr, Sato G. Growth of Madin-Darby canine kidney epithelial cell (MDCK) line in hormone-supplemented, serum-free medium. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3338–3342. [PMC free article] [PubMed]
  • Salomon DS, Liotta LA, Kidwell WR. Differential response to growth factor by rat mammary epithelium plated on different collagen substrata in serum-free medium. Proc Natl Acad Sci U S A. 1981 Jan;78(1):382–386. [PMC free article] [PubMed]
  • Gaush CR, Hard WL, Smith TF. Characterization of an established line of canine kidney cells (MDCK). Proc Soc Exp Biol Med. 1966 Jul;122(3):931–935. [PubMed]
  • Cereijido M, Ehrenfeld J, Meza I, Martínez-Palomo A. Structural and functional membrane polarity in cultured monolayers of MDCK cells. J Membr Biol. 1980;52(2):147–159. [PubMed]
  • Owens RB, Smith HS, Hackett AJ. Epithelial cell cultures from normal glandular tissue of mice. J Natl Cancer Inst. 1974 Jul;53(1):261–269. [PubMed]
  • Dondi P, Muir H. Collagen synthesis and deposition in cartilage during disrupted proteoglycan production. Biochem J. 1976 Oct 15;160(1):117–120. [PMC free article] [PubMed]
  • Telser A, Robinson HC, Dorfman A. The biosynthesis of chondroitin-sulfate protein complex. Proc Natl Acad Sci U S A. 1965 Sep;54(3):912–919. [PMC free article] [PubMed]
  • Kleinman HK, Klebe RJ, Martin GR. Role of collagenous matrices in the adhesion and growth of cells. J Cell Biol. 1981 Mar;88(3):473–485. [PMC free article] [PubMed]
  • Yang J, Richards J, Bowman P, Guzman R, Enami J, McCormick K, Hamamoto S, Pitelka D, Nandi S. Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3401–3405. [PMC free article] [PubMed]
  • Yang J, Richards J, Guzman R, Imagawa W, Nandi S. Sustained growth in primary culture of normal mammary epithelial cells embedded in collagen gels. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2088–2092. [PMC free article] [PubMed]
  • Rindler MJ, Chuman LM, Shaffer L, Saier MH., Jr Retention of differentiated properties in an established dog kidney epithelial cell line (MDCK). J Cell Biol. 1979 Jun;81(3):635–648. [PMC free article] [PubMed]
  • Chambard M, Gabrion J, Mauchamp J. Influence of collagen gel on the orientation of epithelial cell polarity: follicle formation from isolated thyroid cells and from preformed monolayers. J Cell Biol. 1981 Oct;91(1):157–166. [PMC free article] [PubMed]
  • Bennett DC, Armstrong BL, Okada SM. Reconstitution of branching tubules from two cloned mammary cell types in culture. Dev Biol. 1981 Oct 15;87(1):193–199. [PubMed]
  • Geiger B. A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells. Cell. 1979 Sep;18(1):193–205. [PubMed]
  • Dan-Sohkawa M, Fujisawa H. Cell dynamics of the blastulation process in the starfish, Asterina pectinifera. Dev Biol. 1980 Jun 15;77(2):328–339. [PubMed]
  • Nitsch L, Wollman SH. Ultrastructure of intermediate stages in polarity reversal of thyroid epithelium in follicles in suspension culture. J Cell Biol. 1980 Sep;86(3):875–880. [PMC free article] [PubMed]
  • Sugrue SP, Hay ED. Response of basal epithelial cell surface and Cytoskeleton to solubilized extracellular matrix molecules. J Cell Biol. 1981 Oct;91(1):45–54. [PMC free article] [PubMed]
  • Schor SL, Court J. Different mechanisms in the attachment of cells to native and denatured collagen. J Cell Sci. 1979 Aug;38:267–281. [PubMed]
  • Rubin K, Hök M, Obrink B, Timpl R. Substrate adhesion of rat hepatocytes: mechanism of attachment to collagen substrates. Cell. 1981 May;24(2):463–470. [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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...