Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1991 Apr;138(4):961–969.

Expression of neural cell adhesion molecule in normal and neoplastic human neuroendocrine tissues.

L Jin 1, J J Hemperly 1, R V Lloyd 1
PMCID: PMC1886094  PMID: 2012179

Abstract

The neural cell adhesion molecule (N-CAM) is a group of cell surface glycoproteins involved in direct cell--cell adhesion. N-CAM expression in normal and neoplastic tissues was examined with specific antibodies and oligonucleotide probes by immunohistochemistry and in situ hybridization. Most neuroendocrine cells and tumors with secretory granules expressed N-CAM protein and mRNA. Parathyroid adenomas (4) were somewhat unusual, because N-CAM mRNA, but not protein, was detected in some of these benign neoplasms. Most non-neuroendocrine cells and tumors did not express N-CAM, although uterine smooth muscle and an adrenal cortical carcinoma were both positive. Western blots disclosed proteins of 180, 140, and 120 kd in normal adult brain, whereas two pheochromocytomas, a null cell adenoma, and a gastrinoma had proteins of approximately 180 and 140 kd. These results indicate that N-CAM protein and mRNA are widely expressed in neuroendocrine cells and neoplasms. N-CAM oligonucleotide probes as well as antibodies against N-CAM can be used as broad-spectrum neuroendocrine markers. In addition, these molecular probes can be used to examine the role of N-CAM in the development and regulation of neuroendocrine tissues.

Full text

PDF
961

Images in this article

Selected References

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

  1. Akeson R. A., Wujek J. R., Roe S., Warren S. L., Small S. J. Smooth muscle cells transiently express NCAM. Brain Res. 1988 Sep;464(2):107–120. doi: 10.1016/0169-328x(88)90003-4. [DOI] [PubMed] [Google Scholar]
  2. Aletsee-Ufrecht M. C., Langley K., Gratzl O., Gratzl M. Differential expression of the neural cell adhesion molecule NCAM 140 in human pituitary tumors. FEBS Lett. 1990 Oct 15;272(1-2):45–49. doi: 10.1016/0014-5793(90)80445-o. [DOI] [PubMed] [Google Scholar]
  3. Aletsee-Ufrecht M. C., Langley K., Rotsch M., Havemann K., Gratzl M. NCAM: a surface marker for human small cell lung cancer cells. FEBS Lett. 1990 Jul 16;267(2):295–300. doi: 10.1016/0014-5793(90)80948-i. [DOI] [PubMed] [Google Scholar]
  4. Cole S. P., Mirski S., McGarry R. C., Cheng R., Campling B. G., Roder J. C. Differential expression of the Leu-7 antigen on human lung tumor cells. Cancer Res. 1985 Sep;45(9):4285–4290. [PubMed] [Google Scholar]
  5. Crossin K. L., Chuong C. M., Edelman G. M. Expression sequences of cell adhesion molecules. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6942–6946. doi: 10.1073/pnas.82.20.6942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cunningham B. A., Hemperly J. J., Murray B. A., Prediger E. A., Brackenbury R., Edelman G. M. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science. 1987 May 15;236(4803):799–806. doi: 10.1126/science.3576199. [DOI] [PubMed] [Google Scholar]
  7. Doherty P., Barton C. H., Dickson G., Seaton P., Rowett L. H., Moore S. E., Gower H. J., Walsh F. S. Neuronal process outgrowth of human sensory neurons on monolayers of cells transfected with cDNAs for five human N-CAM isoforms. J Cell Biol. 1989 Aug;109(2):789–798. doi: 10.1083/jcb.109.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edelman G. M. Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu Rev Cell Biol. 1986;2:81–116. doi: 10.1146/annurev.cb.02.110186.000501. [DOI] [PubMed] [Google Scholar]
  9. Gennarini G., Hirsch M. R., He H. T., Hirn M., Finne J., Goridis C. Differential expression of mouse neural cell-adhesion molecule (N-CAM) mRNA species during brain development and in neural cell lines. J Neurosci. 1986 Jul;6(7):1983–1990. doi: 10.1523/JNEUROSCI.06-07-01983.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goridis C., Hirn M., Langley O. K., Ghandour S., Gombos G. Brain cell surface glycoproteins identified by monoclonal antibodies. Prog Brain Res. 1983;58:201–208. doi: 10.1016/S0079-6123(08)60021-7. [DOI] [PubMed] [Google Scholar]
  11. Hemperly J. J., Murray B. A., Edelman G. M., Cunningham B. A. Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM. Proc Natl Acad Sci U S A. 1986 May;83(9):3037–3041. doi: 10.1073/pnas.83.9.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoffman S., Edelman G. M. Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5762–5766. doi: 10.1073/pnas.80.18.5762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jorgensen O. S., Bock E. Brain specific synaptosomal membrane proteins demonstrated by crossed immunoelectrophoresis. J Neurochem. 1974 Oct;23(4):879–880. doi: 10.1111/j.1471-4159.1974.tb04419.x. [DOI] [PubMed] [Google Scholar]
  14. Kibbelaar R. E., Moolenaar C. E., Michalides R. J., Bitter-Suermann D., Addis B. J., Mooi W. J. Expression of the embryonal neural cell adhesion molecule N-CAM in lung carcinoma. Diagnostic usefulness of monoclonal antibody 735 for the distinction between small cell lung cancer and non-small cell lung cancer. J Pathol. 1989 Sep;159(1):23–28. doi: 10.1002/path.1711590108. [DOI] [PubMed] [Google Scholar]
  15. Künemund V., Jungalwala F. B., Fischer G., Chou D. K., Keilhauer G., Schachner M. The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions. J Cell Biol. 1988 Jan;106(1):213–223. doi: 10.1083/jcb.106.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Langley O. K., Aletsee-Ufrecht M. C., Grant N. J., Gratzl M. Expression of the neural cell adhesion molecule NCAM in endocrine cells. J Histochem Cytochem. 1989 Jun;37(6):781–791. doi: 10.1177/37.6.2723399. [DOI] [PubMed] [Google Scholar]
  18. Langley O. K., Aletsee M. C., Gratzl M. Endocrine cells share expression of N-CAM with neurones. FEBS Lett. 1987 Aug 10;220(1):108–112. doi: 10.1016/0014-5793(87)80885-2. [DOI] [PubMed] [Google Scholar]
  19. Lanier L. L., Testi R., Bindl J., Phillips J. H. Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med. 1989 Jun 1;169(6):2233–2238. doi: 10.1084/jem.169.6.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lipinski M., Hirsch M. R., Deagostini-Bazin H., Yamada O., Tursz T., Goridis C. Characterization of neural cell adhesion molecules (NCAM) expressed by Ewing and neuroblastoma cell lines. Int J Cancer. 1987 Jul 15;40(1):81–86. doi: 10.1002/ijc.2910400115. [DOI] [PubMed] [Google Scholar]
  21. Lloyd R. V., Coleman K., Fields K., Nath V. Analysis of prolactin and growth hormone production in hyperplastic and neoplastic rat pituitary tissues by the hemolytic plaque assay. Cancer Res. 1987 Feb 15;47(4):1087–1092. [PubMed] [Google Scholar]
  22. Lloyd R. V., Iacangelo A., Eiden L. E., Cano M., Jin L., Grimes M. Chromogranin A and B messenger ribonucleic acids in pituitary and other normal and neoplastic human endocrine tissues. Lab Invest. 1989 Apr;60(4):548–556. [PubMed] [Google Scholar]
  23. Lloyd R. V., Wilson B. S. Specific endocrine tissue marker defined by a monoclonal antibody. Science. 1983 Nov 11;222(4624):628–630. doi: 10.1126/science.6635661. [DOI] [PubMed] [Google Scholar]
  24. Moolenaar C. E., Muller E. J., Schol D. J., Figdor C. G., Bock E., Bitter-Suermann D., Michalides R. J. Expression of neural cell adhesion molecule-related sialoglycoprotein in small cell lung cancer and neuroblastoma cell lines H69 and CHP-212. Cancer Res. 1990 Feb 15;50(4):1102–1106. [PubMed] [Google Scholar]
  25. Murray B. A., Owens G. C., Prediger E. A., Crossin K. L., Cunningham B. A., Edelman G. M. Cell surface modulation of the neural cell adhesion molecule resulting from alternative mRNA splicing in a tissue-specific developmental sequence. J Cell Biol. 1986 Oct;103(4):1431–1439. doi: 10.1083/jcb.103.4.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Navone F., Jahn R., Di Gioia G., Stukenbrok H., Greengard P., De Camilli P. Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J Cell Biol. 1986 Dec;103(6 Pt 1):2511–2527. doi: 10.1083/jcb.103.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Noble M., Albrechtsen M., Møller C., Lyles J., Bock E., Goridis C., Watanabe M., Rutishauser U. Glial cells express N-CAM/D2-CAM-like polypeptides in vitro. Nature. 1985 Aug 22;316(6030):725–728. doi: 10.1038/316725a0. [DOI] [PubMed] [Google Scholar]
  28. Owens G. C., Edelman G. M., Cunningham B. A. Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains. Proc Natl Acad Sci U S A. 1987 Jan;84(1):294–298. doi: 10.1073/pnas.84.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Patel K., Moore S. E., Dickson G., Rossell R. J., Beverley P. C., Kemshead J. T., Walsh F. S. Neural cell adhesion molecule (NCAM) is the antigen recognized by monoclonal antibodies of similar specificity in small-cell lung carcinoma and neuroblastoma. Int J Cancer. 1989 Oct 15;44(4):573–578. doi: 10.1002/ijc.2910440402. [DOI] [PubMed] [Google Scholar]
  30. Patel K., Rossell R. J., Bourne S., Moore S. E., Walsh F. S., Kemshead J. T. Monoclonal antibody UJ13A recognizes the neural cell adhesion molecule (NCAM). Int J Cancer. 1989 Dec 15;44(6):1062–1068. doi: 10.1002/ijc.2910440621. [DOI] [PubMed] [Google Scholar]
  31. Prieto A. L., Crossin K. L., Cunningham B. A., Edelman G. M. Localization of mRNA for neural cell adhesion molecule (N-CAM) polypeptides in neural and nonneural tissues by in situ hybridization. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9579–9583. doi: 10.1073/pnas.86.23.9579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roth J., Zuber C., Wagner P., Taatjes D. J., Weisgerber C., Heitz P. U., Goridis C., Bitter-Suermann D. Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor. Proc Natl Acad Sci U S A. 1988 May;85(9):2999–3003. doi: 10.1073/pnas.85.9.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rutishauser U., Acheson A., Hall A. K., Mann D. M., Sunshine J. The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988 Apr 1;240(4848):53–57. doi: 10.1126/science.3281256. [DOI] [PubMed] [Google Scholar]
  34. Sanes J. R., Schachner M., Covault J. Expression of several adhesive macromolecules (N-CAM, L1, J1, NILE, uvomorulin, laminin, fibronectin, and a heparan sulfate proteoglycan) in embryonic, adult, and denervated adult skeletal muscle. J Cell Biol. 1986 Feb;102(2):420–431. doi: 10.1083/jcb.102.2.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schmechel D., Marangos P. J., Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978 Dec 21;276(5690):834–836. doi: 10.1038/276834a0. [DOI] [PubMed] [Google Scholar]
  36. Thomas P. S., Pietrangeli C. E., Hayashi S., Schachner M., Goridis C., Low M., Kincade P. W. Demonstration of neural cell adhesion molecules on stromal cells that support lymphopoiesis. Leukemia. 1988 Mar;2(3):171–175. [PubMed] [Google Scholar]
  37. Thor G., Probstmeier R., Schachner M. Characterization of the cell adhesion molecules L1, N-CAM and J1 in the mouse intestine. EMBO J. 1987 Sep;6(9):2581–2586. doi: 10.1002/j.1460-2075.1987.tb02548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES