Home LiteratureArticle Details
PMID: 8426113 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Prevention of tumor metastasis formation by anti-variant CD44.

The Journal of experimental medicine ·Vol. 177 ·No. 2 ·1993-02-01 ·Pages 443-55

Seiter S, Arch R, Reber S, Komitowski D, Hofmann M, Ponta H, Herrlich P, Matzku S, Zöller M

Abstract

A splice variant of CD44 (CD44v) originally discovered on metastases of a rat pancreatic adenocarcinoma (BSp73ASML) has been shown by transfection to confer metastatic behavior to nonmetastatic tumor cells (Günthert U., M. Hofmann, W. Rudy, S. Reber, M. Zöller, I. Haussmann, S. Matzku, A. Wenzel, H. Ponta, and P. Herrlich. 1991. Cell. 65:13). A monoclonal antibody (mAb), 1.1ASML, to the metastasis-specific domain of the CD44v molecule retards growth of lymph node and lung metastases of the metastatic tumor line BSp73ASML, and can efficiently prevent formation of metastases by the transfected line. The antibody is only effective when given before lymph node colonization. Anti-CD44v does not downregulate the expression of CD44v, and prevention of metastatic growth by anti-CD44v is not due to activation of any kind of immune defense. We suggest that the mAb interferes with proliferation of metastasizing tumor cells in the draining lymph node, most probably by blocking a ligand interaction. The interference with metastatic spread will greatly facilitate the exploration of the function of CD44v and, in particular, may also open new strategies for the therapy of human metastases.

MeSH Terms
Animals Antibodies, Monoclonal/immunology Antibody-Dependent Cell Cytotoxicity Cell Adhesion Molecules/physiology Cytotoxicity, Immunologic Lung Neoplasms/secondary Lymphatic Metastasis Neoplasm Metastasis Neoplasms, Experimental/pathology Rats Rats, Inbred Strains Receptors, Lymphocyte Homing/chemistry,immunology Structure-Activity Relationship Survival Analysis Time Factors
Chemicals
Antibodies, Monoclonal Cell Adhesion Molecules Receptors, Lymphocyte Homing
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Seiter S
Deutsches Krebsforschungszentrum, Institut für Radiologie und Pathophysiologie, Heidelberg, Germany.
Arch R
Reber S
Komitowski D
Hofmann M
Ponta H
Herrlich P
Matzku S
Zöller M
References (57)
57 references, click to expand
  1. Rat macrophages inhibit natural killer (NK) cell activity against adherent growing target cells.
    Immunobiology. 1982 Dec;163(5):497-510 PMID: 6984420
  2. Characterization of natural cytotoxicity in vitro in a spontaneous rat tumor model.
    J Immunol. 1980 Apr;124(4):1683-90 PMID: 6965955
  3. Cell configuration and adhesive properties of metastasizing and non-metastasizing BSp73 rat adenocarcinoma cells.
    Exp Cell Res. 1986 Jan;162(1):127-41 PMID: 2998841
  4. Clonal analysis of diversity in the BSp73 rat tumor.
    Invasion Metastasis. 1985;5(6):356-70 PMID: 4066207
  5. Differential localization within human kidney of five membrane proteins expressed on acute lymphoblastic leukemia cells.
    J Immunol. 1986 Jan;136(1):118-24 PMID: 2415610
  6. Differential expression of intermediate filament proteins in metastatic and nonmetastatic variants of the BSp73 tumor.
    Cancer Res. 1986 Feb;46(2):785-90 PMID: 3940642
  7. Cytotoxic T-cell precursors against non-immunogenic rat tumors: limiting dilution analysis.
    Int J Cancer. 1986 Jan 15;37(1):133-40 PMID: 3484461
  8. Identification and characterization of the human Pgp-1 glycoprotein.
    Immunogenetics. 1986;23(5):326-32 PMID: 3519447
  9. Homing receptors and the control of lymphocyte migration.
    Immunol Rev. 1986 Jun;91:39-60 PMID: 2426181
  10. Syngeneic monoclonal anti-melanoma antibody that inhibits experimental lung metastasis of B16 melanoma.
    Jpn J Cancer Res. 1986 Jun;77(6):595-601 PMID: 3089994
  11. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man.
    Eur J Immunol. 1986 Oct;16(10):1195-202 PMID: 2429846
  12. Specific cell-adhesion mechanisms determining migration pathways of recirculating lymphocytes.
    Annu Rev Immunol. 1987;5:201-22 PMID: 3297104
  13. Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.
    J Cell Biol. 1987 Aug;105(2):983-90 PMID: 2442176
  14. Inhibition of growth and induction of enzyme activities in a clonal human hepatoma cell line (Li-7A): comparison of the effects of epidermal growth factor and an anti-epidermal growth factor receptor antibody.
    J Cell Physiol. 1988 Jan;134(1):109-16 PMID: 2826500
  15. Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells.
    J Biol Chem. 1988 Mar 25;263(9):4193-201 PMID: 2831221
  16. Antibodies as antigens. The use of mouse monoclonal antibodies to focus human T cells against selected targets.
    J Exp Med. 1988 Feb 1;167(2):345-52 PMID: 2450158
  17. Structural heterogeneity of human Pgp-1 and its relationship with p85.
    Immunogenetics. 1988;27(6):460-4 PMID: 3286493
  18. Antigenic differences between metastatic and nonmetastatic BSp73 rat tumor variants characterized by monoclonal antibodies.
    Cancer Res. 1989 Mar 1;49(5):1294-9 PMID: 2917359
  19. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family.
    Cell. 1989 Mar 24;56(6):1057-62 PMID: 2466575
  20. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins.
    Cell. 1989 Mar 24;56(6):1063-72 PMID: 2466576
  21. Adhesion molecules controlling lymphocyte migration.
    Cell. 1989 Mar 24;56(6):907-10 PMID: 2647304
  22. Depression of nonadaptive immunity after surgical stress: influence on metastatic spread.
    Invasion Metastasis. 1989;9(1):46-68 PMID: 2703300
  23. Structural homology between lymphocyte receptors for high endothelium and class III extracellular matrix receptor.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4654-8 PMID: 2471973
  24. Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules.
    Cancer Res. 1989 Jul 15;49(14):3815-22 PMID: 2736523
  25. Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types.
    J Cell Biol. 1989 Aug;109(2):927-37 PMID: 2474557
  26. Growth factor receptor monoclonal antibodies and cancer immunotherapy.
    J Natl Cancer Inst. 1989 Nov 1;81(21):1600-1 PMID: 2795686
  27. Molecular cloning and expression of Pgp-1. The mouse homolog of the human H-CAM (Hermes) lymphocyte homing receptor.
    J Immunol. 1989 Nov 15;143(10):3390-5 PMID: 2681416
  28. CD44 antibody against In(Lu)-related p80, lymphocyte-homing receptor molecule inhibits the binding of human erythrocytes to T cells.
    J Immunol. 1989 Dec 15;143(12):3944-8 PMID: 2480381
  29. Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression.
    J Immunol. 1990 Mar 1;144(5):1661-70 PMID: 1689752
  30. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose.
    Immunochemistry. 1978 Jul;15(7):429-36 PMID: 30693
  31. Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.
    J Cell Biol. 1992 Oct;119(2):427-38 PMID: 1400584
  32. A rapid method for the separation of functional lymphoid cell populations of human and animal origin on PVP-silica (Percoll) density gradients.
    Scand J Immunol. 1979;10(6):563-73 PMID: 232310
  33. 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):7023-7 PMID: 6787057
  34. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues.
    Immunogenetics. 1982 Mar;15(3):299-312 PMID: 7068174
  35. Biochemical characterisation and localization in brain of a human brain-leucocyte membrane glycoprotein recognised by a monoclonal antibody.
    J Neurochem. 1982 Nov;39(5):1461-6 PMID: 6181207
  36. Murine cell surface glycoproteins. Purification of the polymorphic Pgp-1 antigen and analysis of its expression on macrophages and other myeloid cells.
    J Biol Chem. 1983 Jan 25;258(2):1014-21 PMID: 6822490
  37. Binding of hyaluronic acid to lymphoid cell lines is inhibited by monoclonal antibodies against Pgp-1.
    Exp Cell Res. 1990 Apr;187(2):224-33 PMID: 2180732
  38. Lymphocyte migration into the skin: the role of lymphocyte homing receptor (CD44) and endothelial cell antigen (HECA-452).
    J Invest Dermatol. 1990 Jun;94(6):786-92 PMID: 1693939
  39. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition.
    J Exp Med. 1990 Jul 1;172(1):69-75 PMID: 2193100
  40. CD44 is the principal cell surface receptor for hyaluronate.
    Cell. 1990 Jun 29;61(7):1303-13 PMID: 1694723
  41. The ontogeny of human lymphocyte recirculation: high endothelial cell antigen (HECA-452) and CD44 homing receptor expression in the development of the immune system.
    Eur J Immunol. 1990 Jul;20(7):1483-9 PMID: 2201547
  42. Expression of a human homing receptor (CD44) in lymphoid malignancies and related stages of lymphoid development.
    Leukemia. 1990 May;4(5):383-9 PMID: 2201831
  43. Retardation of metastatic tumor growth after immunization with metastasis-specific monoclonal antibodies.
    Int J Cancer. 1990 Nov 15;46(5):919-27 PMID: 2228320
  44. Suppression of established pulmonary metastases by murine melanoma-specific monoclonal antibodies.
    Int J Cancer. 1991 Jan 2;47(1):148-53 PMID: 1985871
  45. Identification of mRNA that encodes an alternative form of H-CAM(CD44) in lymphoid and nonlymphoid tissues.
    Immunogenetics. 1990;32(6):389-97 PMID: 2272659
  46. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells.
    EMBO J. 1991 Feb;10(2):343-8 PMID: 1991450
  47. A new cell adhesion mechanism involving hyaluronate and CD44.
    Curr Top Microbiol Immunol. 1990;166:87-90 PMID: 2073820
  48. 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):207-21 PMID: 2007624
  49. Suppression of spontaneous melanoma metastasis in scid mice with an antibody to the epidermal growth factor receptor.
    Cancer Res. 1991 Apr 15;51(8):2193-8 PMID: 2009538
  50. Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells.
    J Exp Med. 1991 Jul 1;174(1):1-5 PMID: 2056274
  51. CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines.
    Cancer Res. 1991 Oct 1;51(19):5292-7 PMID: 1717145
  52. CD10 and CD44 genes of leukemic cells and malignant cell lines show no evidence of transformation-related alterations.
    J Cell Physiol. 1991 Sep;148(3):414-20 PMID: 1833412
  53. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody.
    J Exp Med. 1992 Jan 1;175(1):257-66 PMID: 1730918
  54. Establishment and characterization of monoclonal antibodies against an octahedral gallium chelate suitable for immunoscintigraphy with PET.
    J Nucl Med. 1992 Jul;33(7):1366-72 PMID: 1613579
  55. Participation in normal immune responses of a metastasis-inducing splice variant of CD44.
    Science. 1992 Jul 31;257(5070):682-5 PMID: 1496383
  56. Isolation and DNA sequence of a cDNA clone encoding a lymphocyte adhesion receptor for high endothelium.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4659-63 PMID: 2471974
  57. Natural cytotoxicity in lymphatic metastasis. II. In vivo studies with BSp73 variants differing in metastatic capacity.
    Cancer Immunol Immunother. 1984;17(2):106-11 PMID: 6565517
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.177.2.443
Published
1993-02-01
Pages
443-55
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2190906
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.177.2.443 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2