Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Oct 1;174(4):859–866. doi: 10.1084/jem.174.4.859

Distinct effects of two CD44 isoforms on tumor growth in vivo

PMCID: PMC2118964  PMID: 1919439

Abstract

Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

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

  1. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Carter W. G., Wayner E. A. Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells. J Biol Chem. 1988 Mar 25;263(9):4193–4201. [PubMed] [Google Scholar]
  4. Denning S. M., Le P. T., Singer K. H., Haynes B. F. Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation. J Immunol. 1990 Jan 1;144(1):7–15. [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Knudson C. B., Knudson W. Similar epithelial-stromal interactions in the regulation of hyaluronate production during limb morphogenesis and tumor invasion. Cancer Lett. 1990 Jul 16;52(2):113–122. doi: 10.1016/0304-3835(90)90253-t. [DOI] [PubMed] [Google Scholar]
  8. Knudson W., Biswas C., Li X. Q., Nemec R. E., Toole B. P. The role and regulation of tumour-associated hyaluronan. Ciba Found Symp. 1989;143:150-9; discussion 159-69, 281-5. doi: 10.1002/9780470513774.ch10. [DOI] [PubMed] [Google Scholar]
  9. Lacy B. E., Underhill C. B. The hyaluronate receptor is associated with actin filaments. J Cell Biol. 1987 Sep;105(3):1395–1404. doi: 10.1083/jcb.105.3.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lindahl U., Hök M. Glycosaminoglycans and their binding to biological macromolecules. Annu Rev Biochem. 1978;47:385–417. doi: 10.1146/annurev.bi.47.070178.002125. [DOI] [PubMed] [Google Scholar]
  11. MacLeod C. L., Weinroth S. E., Streifinger C., Glaser S. M., Hays E. F. SL12 murine T-lymphoma: a new model for tumor cell heterogeneity. J Natl Cancer Inst. 1985 Apr;74(4):875–882. [PubMed] [Google Scholar]
  12. Miyake K., Medina K. L., Hayashi S., Ono S., Hamaoka T., Kincade P. W. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. doi: 10.1084/jem.171.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Nyormoi O., Klein G., Adams A., Dombos L. Sensitivity to EBV superinfection and IUdR inducibility of hybrid cells formed between a sensitive and a relatively resistant Burkitt lymphoma cell line. Int J Cancer. 1973 Sep 15;12(2):396–408. doi: 10.1002/ijc.2910120211. [DOI] [PubMed] [Google Scholar]
  15. Picker L. J., Medeiros L. J., Weiss L. M., Warnke R. A., Butcher E. C. Expression of lymphocyte homing receptor antigen in non-Hodgkin's lymphoma. Am J Pathol. 1988 Mar;130(3):496–504. [PMC free article] [PubMed] [Google Scholar]
  16. Quackenbush E. J., Vera S., Greaves A., Letarte M. Confirmation by peptide sequence and co-expression on various cell types of the identity of CD44 and P85 glycoprotein. Mol Immunol. 1990 Oct;27(10):947–955. doi: 10.1016/0161-5890(90)90117-i. [DOI] [PubMed] [Google Scholar]
  17. Ruoslahti E. Proteoglycans in cell regulation. J Biol Chem. 1989 Aug 15;264(23):13369–13372. [PubMed] [Google Scholar]
  18. Sher B. T., Bargatze R., Holzmann B., Gallatin W. M., Matthews D., Wu N., Picker L., Butcher E. C., Weissman I. L. Homing receptors and metastasis. Adv Cancer Res. 1988;51:361–390. doi: 10.1016/s0065-230x(08)60226-2. [DOI] [PubMed] [Google Scholar]
  19. Shimizu Y., Van Seventer G. A., Siraganian R., Wahl L., Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed] [Google Scholar]
  20. Stamenkovic I., Amiot M., Pesando J. M., Seed B. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057–1062. doi: 10.1016/0092-8674(89)90638-7. [DOI] [PubMed] [Google Scholar]
  21. Stamenkovic I., Aruffo A., Amiot M., Seed B. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J. 1991 Feb;10(2):343–348. doi: 10.1002/j.1460-2075.1991.tb07955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Toole B. P., Biswas C., Gross J. Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6299–6303. doi: 10.1073/pnas.76.12.6299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Underhill C. B. The interaction of hyaluronate with the cell surface: the hyaluronate receptor and the core protein. Ciba Found Symp. 1989;143:87-99; discussion 100-6, 281-5. doi: 10.1002/9780470513774.ch6. [DOI] [PubMed] [Google Scholar]
  24. Webb D. S., Shimizu Y., Van Seventer G. A., Shaw S., Gerrard T. L. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science. 1990 Sep 14;249(4974):1295–1297. doi: 10.1126/science.1697984. [DOI] [PubMed] [Google Scholar]
  25. Weigel P. H., Frost S. J., LeBoeuf R. D., McGary C. T. The specific interaction between fibrin(ogen) and hyaluronan: possible consequences in haemostasis, inflammation and wound healing. Ciba Found Symp. 1989;143:248-61; discussion 261-4, 281-5. doi: 10.1002/9780470513774.ch15. [DOI] [PubMed] [Google Scholar]
  26. West D. C., Kumar S. Hyaluronan and angiogenesis. Ciba Found Symp. 1989;143:187-201; discussion 201-7, 281-5. doi: 10.1002/9780470513774.ch12. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES