Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Apr;81(8):2426–2430. doi: 10.1073/pnas.81.8.2426

Increased adhesiveness of Down syndrome fetal fibroblasts in vitro.

T C Wright, R W Orkin, M Destrempes, D M Kurnit
PMCID: PMC345073  PMID: 6232609

Abstract

We compared the in vitro rate of divalent cation-independent aggregation of fibroblasts derived from abortuses with normal karyotypes and with trisomy 21 (Down syndrome). Fibroblasts from five lung and two of three cardiac cultures from subjects with Down syndrome aggregated more rapidly than matched fibroblasts from normal controls or lung fibroblasts from an abortus with trisomy 13. In contrast, skin fibroblasts derived from the trisomy 21 subjects had low rates of aggregation. The high rates of aggregation of trisomy 21 lung fibroblasts were not affected by hyaluronidase treatment. Lung fibroblasts from both normal and Down syndrome subjects had similar membrane polarization values in an assay using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Thus, the increased aggregation rate we observed for trisomy 21 fibroblasts was restricted to specific fibroblast cultures, was not mediated by hyaluronic acid or gross membrane lipid alterations, and was specific for trisomy of chromosome 21. As illustrated in computer simulations presented elsewhere, increased intercellular adhesiveness during organogenesis could explain the frequent occurrence of malformations, including pulmonary hypoplasia and congenital heart defects, in Down syndrome.

Full text

PDF
2429

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bartley J. A., Epstein C. J. Gene dosage effect for glycinamide ribonucleotide synthetase in human fibroblasts trisomic for chromosome 21. Biochem Biophys Res Commun. 1980 Apr 29;93(4):1286–1289. doi: 10.1016/0006-291x(80)90629-4. [DOI] [PubMed] [Google Scholar]
  2. Brackenbury R., Rutishauser U., Edelman G. M. Distinct calcium-independent and calcium-dependent adhesion systems of chicken embryo cells. Proc Natl Acad Sci U S A. 1981 Jan;78(1):387–391. doi: 10.1073/pnas.78.1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buskirk D. R., Thiery J. P., Rutishauser U., Edelman G. M. Antibodies to a neural cell adhesion molecule disrupt histogenesis in cultured chick retinae. Nature. 1980 Jun 12;285(5765):488–489. doi: 10.1038/285488a0. [DOI] [PubMed] [Google Scholar]
  4. Cooney T. P., Thurlbeck W. M. Pulmonary hypoplasia in Down's syndrome. N Engl J Med. 1982 Nov 4;307(19):1170–1173. doi: 10.1056/NEJM198211043071902. [DOI] [PubMed] [Google Scholar]
  5. Feaster W. W., Kwok L. W., Epstein C. J. Dosage effects for superoxide dismutase-1 in nucleated cells aneuploid for chromosome 21. Am J Hum Genet. 1977 Nov;29(6):563–570. [PMC free article] [PubMed] [Google Scholar]
  6. Frazier W., Glaser L. Surface components and cell recognition. Annu Rev Biochem. 1979;48:491–523. doi: 10.1146/annurev.bi.48.070179.002423. [DOI] [PubMed] [Google Scholar]
  7. Hay D. A., Low F. N. The fusion of dorsal and ventral endocardial cushions in the embryonic chick heart: a study in fine structure. Am J Anat. 1972 Jan;133(1):1–23. doi: 10.1002/aja.1001330102. [DOI] [PubMed] [Google Scholar]
  8. Hoover R. L., Bhalla D. K., Yanovich S., Inbar M., Karnovsky M. J. Effects of linoleic acid on capping, lectin mediated mitogenesis, surface antigen expression, and fluorescent polarization in lymphocytes and BHK cells. J Cell Physiol. 1980 Jun;103(3):399–406. doi: 10.1002/jcp.1041030305. [DOI] [PubMed] [Google Scholar]
  9. Hoover R. L., Lynch R. D., Karnovsky M. J. Decrease in adhesion of cells cultured in polyunsaturated fatty acids. Cell. 1977 Sep;12(1):295–300. doi: 10.1016/0092-8674(77)90207-0. [DOI] [PubMed] [Google Scholar]
  10. JACOBS P. A., BAIKIE A. G., COURT BROWN W. M., STRONG J. A. The somatic chromosomes in mongolism. Lancet. 1959 Apr 4;1(7075):710–710. doi: 10.1016/s0140-6736(59)91892-6. [DOI] [PubMed] [Google Scholar]
  11. Juliano R. L., Gagalang E. The effect of membrane-fluidizing agents on the adhesion of CHO cells. J Cell Physiol. 1979 Mar;98(3):483–489. doi: 10.1002/jcp.1040980307. [DOI] [PubMed] [Google Scholar]
  12. Kano K., Chan M., Ruddle F. H., Milgrom F. Reactions of human alloantisera with man-mouse hybrid cells carrying chromosome 21. Transplant Proc. 1979 Mar;11(1):1098–1101. [PubMed] [Google Scholar]
  13. Klausner R. D., Bhalla D. K., Dragsten P., Hoover R. L., Karnovsky M. J. Model for capping derived from inhibition of surface receptor capping by free fatty acids. Proc Natl Acad Sci U S A. 1980 Jan;77(1):437–441. doi: 10.1073/pnas.77.1.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurnit D. M. Down syndrome: gene dosage at the transcriptional level in skin fibroblasts. Proc Natl Acad Sci U S A. 1979 May;76(5):2372–2375. doi: 10.1073/pnas.76.5.2372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LEJEUNE J., GAUTIER M., TURPIN R. Etude des chromosomes somatiques de neuf enfants mongoliens. C R Hebd Seances Acad Sci. 1959 Mar 16;248(11):1721–1722. [PubMed] [Google Scholar]
  16. Markwald R. R., Fitzharris T. P., Manasek F. J. Structural development of endocardial cushions. Am J Anat. 1977 Jan;148(1):85–119. doi: 10.1002/aja.1001480108. [DOI] [PubMed] [Google Scholar]
  17. Orkin R. W., Toole B. P. Isolation and characterization of hyaluronidase from cultures of chick embryo skin- and muscle-derived fibroblasts. J Biol Chem. 1980 Feb 10;255(3):1036–1042. [PubMed] [Google Scholar]
  18. Orkin R. W., Underhill C. B., Toole B. P. Hyaluronate degradation in 3T3 and simian virus-transformed 3T3 cells. J Biol Chem. 1982 May 25;257(10):5821–5826. [PubMed] [Google Scholar]
  19. Park S. C., Mathews R. A., Zuberbuhler J. R., Rowe R. D., Neches W. H., Lenox C. C. Down syndrome with congenital heart malformation. Am J Dis Child. 1977 Jan;131(1):29–33. doi: 10.1001/archpedi.1977.02120140031003. [DOI] [PubMed] [Google Scholar]
  20. Patterson D., Graw S., Jones C. Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21. Proc Natl Acad Sci U S A. 1981 Jan;78(1):405–409. doi: 10.1073/pnas.78.1.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. ROWE R. D., UCHIDA I. A. Cardiac malformation in mongolism: a prospective study of 184 mongoloid children. Am J Med. 1961 Nov;31:726–735. doi: 10.1016/0002-9343(61)90157-7. [DOI] [PubMed] [Google Scholar]
  22. Rutishauser U., Gall W. E., Edelman G. M. Adhesion among neural cells of the chick embryo. IV. Role of the cell surface molecule CAM in the formation of neurite bundles in cultures of spinal ganglia. J Cell Biol. 1978 Nov;79(2 Pt 1):382–393. doi: 10.1083/jcb.79.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shinitzky M., Inbar M. Difference in microviscosity induced by different cholesterol levels in the surface membrane lipid layer of normal lymphocytes and malignant lymphoma cells. J Mol Biol. 1974 Jan 5;85(4):603–615. doi: 10.1016/0022-2836(74)90318-0. [DOI] [PubMed] [Google Scholar]
  24. Sichitiu S., Sinet P. M., Lejeune J., Frézal J. Surdosage de la forme dimérique de l'indophénoloxydase dans la trisomie 21, secondaire au surdosage génique. Humangenetik. 1974 Jun 26;23(1):65–72. doi: 10.1007/BF00295684. [DOI] [PubMed] [Google Scholar]
  25. Tandon R., Edwards J. E. Cardiac malformations associated with Down's syndrome. Circulation. 1973 Jun;47(6):1349–1355. doi: 10.1161/01.cir.47.6.1349. [DOI] [PubMed] [Google Scholar]
  26. Toole B. P., Gross J. The extracellular matrix of the regenerating newt limb: synthesis and removal of hyaluronate prior to differentiation. Dev Biol. 1971 May;25(1):57–77. doi: 10.1016/0012-1606(71)90019-4. [DOI] [PubMed] [Google Scholar]
  27. Underhill C., Dorfman A. The role of hyaluronic acid in intercellular adhesion of cultured mouse cells. Exp Cell Res. 1978 Nov;117(1):155–164. doi: 10.1016/0014-4827(78)90438-x. [DOI] [PubMed] [Google Scholar]
  28. VAN MIEROP L. H., ALLEY R. D., KAUSEL H. W., STRANAHAN A. The anatomy and embryology of endocardial cushion defects. J Thorac Cardiovasc Surg. 1962 Jan;43:71–83. [PubMed] [Google Scholar]
  29. Vora S., Francke U. Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3738–3742. doi: 10.1073/pnas.78.6.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Weeks G. The manipulation of the fatty acid composition of Dictyostelium discoideum and its effect on cell differentiation. Biochim Biophys Acta. 1976 Oct 21;450(1):21–32. doi: 10.1016/0005-2760(76)90295-2. [DOI] [PubMed] [Google Scholar]
  31. Weil J., Epstein L. B., Epstein C. J. Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays. J Interferon Res. 1980 Fall;1(1):111–124. doi: 10.1089/jir.1980.1.111. [DOI] [PubMed] [Google Scholar]
  32. Wright T. C., Smith B., Ware B. R., Karnovsky M. J. The role of negative charge in spontaneous aggregation of transformed and untransformed cell lines. J Cell Sci. 1980 Oct;45:99–117. doi: 10.1242/jcs.45.1.99. [DOI] [PubMed] [Google Scholar]
  33. Wright T. C., Ukena T. E., Campbell R., Karnovsky M. J. Rates of aggregation, loss of anchorage dependence, and tumorigenicity of cultured cells. Proc Natl Acad Sci U S A. 1977 Jan;74(1):258–262. doi: 10.1073/pnas.74.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES