Skip to main content
NCBI home page
Gut logoLink to Gut
. 1996 Apr;38(4):507–512. doi: 10.1136/gut.38.4.507

Expression of CD44 and its variants on gastric epithelial cells of patients with Helicobacter pylori colonisation.

X Fan 1, A Long 1, M Goggins 1, X Fan 1, P W Keeling 1, D Kelleher 1
PMCID: PMC1383105  PMID: 8707078

Abstract

BACKGROUND--Studies have suggested that expression of the adhesion molecule CD44 may be of prognostic importance in gastric cancer. In addition, there is strong evidence that Helicobacter pylori has a role in gastric cancer. AIMS--To determine the expression of CD44 and its variants (v6, v9) and HLA class II molecules on human gastric epithelial cell and intraepithelial lymphocytes in patients with and without H pylori infection. PATIENTS--Eighteen patients (seven men and 11 women) attending for endoscopic evaluation because of upper gastrointestinal symptoms were included. An additional 10 patients (five men and five women) were analysed for CD44 variant expression). METHODS--Biopsy specimens were taken from the gastric antrum during endoscopy. Gastric epithelial cells and intraepithelial lymphocytes were examined by two colour flow cytometry and compared in patients with and without H pylori infection. RESULTS--Expression of CD44 and its variants (CD44 v9) was increased in epithelial cells but not in intraepithelial lymphocytes. Both epithelial cells and intraepithelial lymphocytes expressed higher levels of HLA class II molecules (DR and DP), possibly as a result of local cytokine production. Furthermore, results showed upregulation of CD44 on a gastric epithelial cell line (AGS) by cytokines and peripheral blood mononuclear cell supernatant. CONCLUSIONS--These data suggest that H pylori, either directly or through a local inflammatory response, is responsible for increased expression of CD44 and its variant CD44 v9. These data are of potential importance in relation to increased expression of CD44 and CD44 v9 on gastric carcinoma.

Full text

PDF
507

Selected References

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

  1. Brown T. A., Bouchard T., St John T., Wayner E., Carter W. G. Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons. J Cell Biol. 1991 Apr;113(1):207–221. doi: 10.1083/jcb.113.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crabtree J. E., Shallcross T. M., Heatley R. V., Wyatt J. I. Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis. Gut. 1991 Dec;32(12):1473–1477. doi: 10.1136/gut.32.12.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dougherty G. J., Cooper D. L., Memory J. F., Chiu R. K. Ligand binding specificity of alternatively spliced CD44 isoforms. Recognition and binding of hyaluronan by CD44R1. J Biol Chem. 1994 Mar 25;269(12):9074–9078. [PubMed] [Google Scholar]
  4. Fan X. G., Kelleher D., Fan X. J., Xia H. X., Keeling P. W. Helicobacter pylori increases proliferation of gastric epithelial cells. Gut. 1996 Jan;38(1):19–22. doi: 10.1136/gut.38.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fan X. J., Chua A., O'Connell M. A., Kelleher D., Keeling P. W. Interferon-gamma and tumour necrosis factor production in patients with Helicobacter pylori infection. Ir J Med Sci. 1993 Oct;162(10):408–411. doi: 10.1007/BF02996319. [DOI] [PubMed] [Google Scholar]
  6. Fan X., Long A., Fan X., Keeling P. W., Kelleher D. Adhesion molecule expression on gastric intra-epithelial lymphocytes of patients with Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1995 Jun;7(6):541–546. [PubMed] [Google Scholar]
  7. Fox S. B., Fawcett J., Jackson D. G., Collins I., Gatter K. C., Harris A. L., Gearing A., Simmons D. L. Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms. Cancer Res. 1994 Aug 15;54(16):4539–4546. [PubMed] [Google Scholar]
  8. Galandrini R., Albi N., Tripodi G., Zarcone D., Terenzi A., Moretta A., Grossi C. E., Velardi A. Antibodies to CD44 trigger effector functions of human T cell clones. J Immunol. 1993 May 15;150(10):4225–4235. [PubMed] [Google Scholar]
  9. Guo Y., Ma J., Wang J., Che X., Narula J., Bigby M., Wu M., Sy M. S. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res. 1994 Mar 15;54(6):1561–1565. [PubMed] [Google Scholar]
  10. Günthert U., Hofmann M., Rudy W., Reber S., Zöller M., Haussmann I., Matzku S., Wenzel A., Ponta H., Herrlich P. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991 Apr 5;65(1):13–24. doi: 10.1016/0092-8674(91)90403-l. [DOI] [PubMed] [Google Scholar]
  11. Haynes B. F., Hale L. P., Patton K. L., Martin M. E., McCallum R. M. Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis. Arthritis Rheum. 1991 Nov;34(11):1434–1443. doi: 10.1002/art.1780341115. [DOI] [PubMed] [Google Scholar]
  12. Haynes B. F., Telen M. J., Hale L. P., Denning S. M. CD44--a molecule involved in leukocyte adherence and T-cell activation. Immunol Today. 1989 Dec;10(12):423–428. doi: 10.1016/0167-5699(89)90040-6. [DOI] [PubMed] [Google Scholar]
  13. Horst E., Meijer C. J., Radaszkiewicz T., Ossekoppele G. J., Van Krieken J. H., Pals S. T. Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). Leukemia. 1990 Aug;4(8):595–599. [PubMed] [Google Scholar]
  14. Hughes E. N., Mengod G., August J. T. Murine cell surface glycoproteins. Characterization of a major component of 80,000 daltons as a polymorphic differentiation antigen of mesenchymal cells. J Biol Chem. 1981 Jul 10;256(13):7023–7027. [PubMed] [Google Scholar]
  15. Joensuu H., Klemi P. J., Toikkanen S., Jalkanen S. Glycoprotein CD44 expression and its association with survival in breast cancer. Am J Pathol. 1993 Sep;143(3):867–874. [PMC free article] [PubMed] [Google Scholar]
  16. Joensuu H., Ristamäki R., Klemi P. J., Jalkanen S. Lymphocyte homing receptor (CD44) expression is associated with poor prognosis in gastrointestinal lymphoma. Br J Cancer. 1993 Aug;68(2):428–432. doi: 10.1038/bjc.1993.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kelleher D., Murphy A., Lynch S., O'Farrelly C. Adhesion molecules utilized in binding of intraepithelial lymphocytes to human enterocytes. Eur J Immunol. 1994 Apr;24(4):1013–1016. doi: 10.1002/eji.1830240437. [DOI] [PubMed] [Google Scholar]
  18. Mackay C. R., Terpe H. J., Stauder R., Marston W. L., Stark H., Günthert U. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol. 1994 Jan;124(1-2):71–82. doi: 10.1083/jcb.124.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mackay C. R., Terpe H. J., Stauder R., Marston W. L., Stark H., Günthert U. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol. 1994 Jan;124(1-2):71–82. doi: 10.1083/jcb.124.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Madrigal L., Lynch S., Feighery C., Weir D., Kelleher D., O'Farrelly C. Flow cytometric analysis of surface major histocompatibility complex class II expression on human epithelial cells prepared from small intestinal biopsies. J Immunol Methods. 1993 Feb 3;158(2):207–214. doi: 10.1016/0022-1759(93)90216-t. [DOI] [PubMed] [Google Scholar]
  21. Marshall B. J., Warren J. R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984 Jun 16;1(8390):1311–1315. doi: 10.1016/s0140-6736(84)91816-6. [DOI] [PubMed] [Google Scholar]
  22. Mayer B., Jauch K. W., Günthert U., Figdor C. G., Schildberg F. W., Funke I., Johnson J. P. De-novo expression of CD44 and survival in gastric cancer. Lancet. 1993 Oct 23;342(8878):1019–1022. doi: 10.1016/0140-6736(93)92879-x. [DOI] [PubMed] [Google Scholar]
  23. Miyake K., Underhill C. B., Lesley J., Kincade P. W. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990 Jul 1;172(1):69–75. doi: 10.1084/jem.172.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
  25. Parsonnet J., Friedman G. D., Vandersteen D. P., Chang Y., Vogelman J. H., Orentreich N., Sibley R. K. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. doi: 10.1056/NEJM199110173251603. [DOI] [PubMed] [Google Scholar]
  26. Rosenberg W. M., Prince C., Kaklamanis L., Fox S. B., Jackson D. G., Simmons D. L., Chapman R. W., Trowell J. M., Jewell D. P., Bell J. I. Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not colonic Crohn's disease. Lancet. 1995 May 13;345(8959):1205–1209. doi: 10.1016/s0140-6736(95)91991-0. [DOI] [PubMed] [Google Scholar]
  27. Sallusto F., Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994 Apr 1;179(4):1109–1118. doi: 10.1084/jem.179.4.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Seiter S., Arch R., Reber S., Komitowski D., Hofmann M., Ponta H., Herrlich P., Matzku S., Zöller M. Prevention of tumor metastasis formation by anti-variant CD44. J Exp Med. 1993 Feb 1;177(2):443–455. doi: 10.1084/jem.177.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Spencer J., Finn T., Isaacson P. G. Expression of HLA-DR antigens on epithelium associated with lymphoid tissue in the human gastrointestinal tract. Gut. 1986 Feb;27(2):153–157. doi: 10.1136/gut.27.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tanabe K. K., Ellis L. M., Saya H. Expression of CD44R1 adhesion molecule in colon carcinomas and metastases. Lancet. 1993 Mar 20;341(8847):725–726. doi: 10.1016/0140-6736(93)90490-8. [DOI] [PubMed] [Google Scholar]
  31. Wee A., Teh M., Kang J. Y. Association of Helicobacter pylori with HLA-DR antigen expression in gastritis. J Clin Pathol. 1992 Jan;45(1):30–33. doi: 10.1136/jcp.45.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES