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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
. 1995 Dec 19;92(26):12240–12244. doi: 10.1073/pnas.92.26.12240

The stem cell antigen CD34 functions as a regulator of hemopoietic cell adhesion.

L Healy 1, G May 1, K Gale 1, F Grosveld 1, M Greaves 1, T Enver 1
PMCID: PMC40332  PMID: 8618877

Abstract

Although the CD34 antigen is widely used in the identification and purification of hemopoietic stem and progenitor cells, its function within hemopoiesis is unknown. We have investigated this issue by ectopically expressing human (hu) CD34 on the surface of murine hemopoietic cells. Forced expression of hu-CD34 in the thymocytes of transgenic mice did not appear to affect the development, maturation, or distribution of murine T cells but did significantly increase their ability to adhere to bone marrow stromal layers of human but not mouse origin. Ectopic expression of hu-CD34 on murine 416B cells, a multipotential progenitor that expresses murine CD34, yielded similar results. In both cases hu-CD34-dependent adhesion was enhanced by molecular engagement of the hu-CD34 protein using anti-CD34 antibodies. These results provide evidence that CD34 promotes the adhesive interactions of hemopoietic cells with the stromal microenvironment of the bone marrow thereby implicating CD34 in regulation and compartmentalization of stem cells. We propose that CD34 regulates these processes in part via an indirect mechanism, signaling changes in cellular adhesion in response to molecular recognition of an as yet unidentified stromal CD34 counterreceptor or ligand.

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Selected References

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  1. Acheson A., Sunshine J. L., Rutishauser U. NCAM polysialic acid can regulate both cell-cell and cell-substrate interactions. J Cell Biol. 1991 Jul;114(1):143–153. doi: 10.1083/jcb.114.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. Ardman B., Sikorski M. A., Staunton D. E. CD43 interferes with T-lymphocyte adhesion. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5001–5005. doi: 10.1073/pnas.89.11.5001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baumheter S., Singer M. S., Henzel W., Hemmerich S., Renz M., Rosen S. D., Lasky L. A. Binding of L-selectin to the vascular sialomucin CD34. Science. 1993 Oct 15;262(5132):436–438. doi: 10.1126/science.7692600. [DOI] [PubMed] [Google Scholar]
  5. Baumhueter S., Dybdal N., Kyle C., Lasky L. A. Global vascular expression of murine CD34, a sialomucin-like endothelial ligand for L-selectin. Blood. 1994 Oct 15;84(8):2554–2565. [PubMed] [Google Scholar]
  6. Berenson R. J., Bensinger W. I., Hill R. S., Andrews R. G., Garcia-Lopez J., Kalamasz D. F., Still B. J., Spitzer G., Buckner C. D., Bernstein I. D. Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. Blood. 1991 Apr 15;77(8):1717–1722. [PubMed] [Google Scholar]
  7. Brown J., Greaves M. F., Molgaard H. V. The gene encoding the stem cell antigen, CD34, is conserved in mouse and expressed in haemopoietic progenitor cell lines, brain, and embryonic fibroblasts. Int Immunol. 1991 Feb;3(2):175–184. doi: 10.1093/intimm/3.2.175. [DOI] [PubMed] [Google Scholar]
  8. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  9. Clark B. R., Gallagher J. T., Dexter T. M. Cell adhesion in the stromal regulation of haemopoiesis. Baillieres Clin Haematol. 1992 Jul;5(3):619–652. doi: 10.1016/s0950-3536(11)80010-7. [DOI] [PubMed] [Google Scholar]
  10. Delia D., Lampugnani M. G., Resnati M., Dejana E., Aiello A., Fontanella E., Soligo D., Pierotti M. A., Greaves M. F. CD34 expression is regulated reciprocally with adhesion molecules in vascular endothelial cells in vitro. Blood. 1993 Feb 15;81(4):1001–1008. [PubMed] [Google Scholar]
  11. Dexter T. M., Allen T. D., Scott D., Teich N. M. Isolation and characterisation of a bipotential haematopoietic cell line. Nature. 1979 Feb 8;277(5696):471–474. doi: 10.1038/277471a0. [DOI] [PubMed] [Google Scholar]
  12. Fina L., Molgaard H. V., Robertson D., Bradley N. J., Monaghan P., Delia D., Sutherland D. R., Baker M. A., Greaves M. F. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990 Jun 15;75(12):2417–2426. [PubMed] [Google Scholar]
  13. Furley A. J., Reeves B. R., Mizutani S., Altass L. J., Watt S. M., Jacob M. C., van den Elsen P., Terhorst C., Greaves M. F. Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines. Blood. 1986 Nov;68(5):1101–1107. [PubMed] [Google Scholar]
  14. Gordon M. Y., Dowding C. R., Riley G. P., Greaves M. F. Characterisation of stroma-dependent blast colony-forming cells in human marrow. J Cell Physiol. 1987 Jan;130(1):150–156. doi: 10.1002/jcp.1041300121. [DOI] [PubMed] [Google Scholar]
  15. Greaves D. R., Wilson F. D., Lang G., Kioussis D. Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell. 1989 Mar 24;56(6):979–986. doi: 10.1016/0092-8674(89)90631-4. [DOI] [PubMed] [Google Scholar]
  16. Greaves M. F., Brown J., Molgaard H. V., Spurr N. K., Robertson D., Delia D., Sutherland D. R. Molecular features of CD34: a hemopoietic progenitor cell-associated molecule. Leukemia. 1992;6 (Suppl 1):31–36. [PubMed] [Google Scholar]
  17. Itoh K., Tezuka H., Sakoda H., Konno M., Nagata K., Uchiyama T., Uchino H., Mori K. J. Reproducible establishment of hemopoietic supportive stromal cell lines from murine bone marrow. Exp Hematol. 1989 Feb;17(2):145–153. [PubMed] [Google Scholar]
  18. Krause D. S., Ito T., Fackler M. J., Smith O. M., Collector M. I., Sharkis S. J., May W. S. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. Blood. 1994 Aug 1;84(3):691–701. [PubMed] [Google Scholar]
  19. Lasky L. A., Singer M. S., Dowbenko D., Imai Y., Henzel W. J., Grimley C., Fennie C., Gillett N., Watson S. R., Rosen S. D. An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell. 1992 Jun 12;69(6):927–938. doi: 10.1016/0092-8674(92)90612-g. [DOI] [PubMed] [Google Scholar]
  20. Majdic O., Stöckl J., Pickl W. F., Bohuslav J., Strobl H., Scheinecker C., Stockinger H., Knapp W. Signaling and induction of enhanced cytoadhesiveness via the hematopoietic progenitor cell surface molecule CD34. Blood. 1994 Mar 1;83(5):1226–1234. [PubMed] [Google Scholar]
  21. Norton J., Sloane J. P., Delia D., Greaves M. F. Reciprocal expression of CD34 and cell adhesion molecule ELAM-1 on vascular endothelium in acute cutaneous graft-versus-host disease. J Pathol. 1993 Jun;170(2):173–177. doi: 10.1002/path.1711700213. [DOI] [PubMed] [Google Scholar]
  22. Oxley S. M., Sackstein R. Detection of an L-selectin ligand on a hematopoietic progenitor cell line. Blood. 1994 Nov 15;84(10):3299–3306. [PubMed] [Google Scholar]
  23. Papayannopoulou T., Nakamoto B. Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9374–9378. doi: 10.1073/pnas.90.20.9374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Siena S., Bregni M., Brando B., Belli N., Ravagnani F., Gandola L., Stern A. C., Lansdorp P. M., Bonadonna G., Gianni A. M. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood. 1991 Jan 15;77(2):400–409. [PubMed] [Google Scholar]
  25. Simmons D. L., Satterthwaite A. B., Tenen D. G., Seed B. Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells. J Immunol. 1992 Jan 1;148(1):267–271. [PubMed] [Google Scholar]
  26. Streeter P. R., Rouse B. T., Butcher E. C. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol. 1988 Nov;107(5):1853–1862. doi: 10.1083/jcb.107.5.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sutherland D. R., Watt S. M., Dowden G., Karhi K., Baker M. A., Greaves M. F., Smart J. E. Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34. Leukemia. 1988 Dec;2(12):793–803. [PubMed] [Google Scholar]
  28. Torok-Storb B. Cellular interactions. Blood. 1988 Aug;72(2):373–385. [PubMed] [Google Scholar]
  29. Traoré Y., Hirn J. Certain anti-CD34 monoclonal antibodies induce homotypic adhesion of leukemic cell lines in a CD18-dependent and a CD18-independent way. Eur J Immunol. 1994 Oct;24(10):2304–2311. doi: 10.1002/eji.1830241007. [DOI] [PubMed] [Google Scholar]

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