Home LiteratureArticle Details
PMID: 7504687 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression.

The Journal of clinical investigation ·Vol. 92 ·No. 6 ·1993-12-00 ·Pages 2569-76

Arteaga CL, Hurd SD, Winnier AR, Johnson MD, Fendly BM, Forbes JT

Abstract

TGF-beta effects on angiogenesis, stroma formation, and immune function suggest its possible involvement in tumor progression. This hypothesis was tested using the 2G7 IgG2b, which neutralizes TGF-beta 1, -beta 2, and -beta 3, and the MDA-231 human breast cancer cell line. Inoculation of these cells in athymic mice decreases mouse spleen natural killer (NK) cell activity. Intraperitoneal injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing anti-TGF-beta 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and control tumors were identical. Intraperitoneal administration of 2G7 resulted in a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231 primary tumor or metastases formation, nor did it stimulate NK cell-mediated cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned medium from MDA-231 cells inhibited the NK cell activity of human blood lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-beta 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF-beta in the progression of mammary carcinomas by suppressing host immune surveillance.

MeSH Terms
Animals Antibodies/pharmacology Breast Neoplasms/blood supply,immunology,pathology Cell Division Collagen/analysis,metabolism Cytotoxicity, Immunologic Factor VIII/analysis,metabolism Female Humans Immunoglobulin G/classification,pharmacology Killer Cells, Natural/immunology Lung Neoplasms/immunology,prevention & control,secondary Mice Mice, Nude Neoplasm Metastasis Neoplasm Transplantation Neovascularization, Pathologic/prevention & control Recombinant Proteins/pharmacology Spleen/immunology Transforming Growth Factor beta/immunology,pharmacology,physiology Transplantation, Heterologous Tumor Cells, Cultured
Chemicals
Antibodies Immunoglobulin G Recombinant Proteins Transforming Growth Factor beta Factor VIII Collagen
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Arteaga C L
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Hurd S D
Winnier A R
Johnson M D
Fendly B M
Forbes J T
References (37)
37 references, click to expand
  1. Growth factors in the regulation of pericellular proteolysis: a review.
    Cancer Res. 1989 May 15;49(10):2533-53 PMID: 2469534
  2. Expression of growth factors and oncogenes in normal and tumor-derived human mammary epithelial cells.
    Cancer Res. 1988 Dec 15;48(24 Pt 1):7041-7 PMID: 3191480
  3. Differential regulation of expression of three transforming growth factor beta species in human breast cancer cell lines by estradiol.
    Cancer Res. 1990 Jan 15;50(2):299-303 PMID: 2295070
  4. A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune surveillance.
    Proc Natl Acad Sci U S A. 1990 Feb;87(4):1486-90 PMID: 2137615
  5. Approaches to studying the role of growth factors in the progression of breast tumours from the steroid sensitive to insensitive state.
    J Steroid Biochem. 1989;34(1-6):133-8 PMID: 2696842
  6. Transcripts for transforming growth factors in human breast cancer: clinical correlates.
    Br J Cancer. 1990 Apr;61(4):612-7 PMID: 2331446
  7. Interaction of growth factors during progression towards steroid independence in T-47-D human breast cancer cells.
    J Cell Biochem. 1990 Jul;43(3):199-211 PMID: 2199468
  8. The autocrine production of transforming growth factor-beta 1 during lymphocyte activation. A study with a monoclonal antibody-based ELISA.
    J Immunol. 1990 Sep 1;145(5):1415-22 PMID: 2384664
  9. Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7678-82 PMID: 2217201
  10. Immunoregulatory role of transforming growth factor beta (TGF-beta) in development of killer cells: comparison of active and latent TGF-beta 1.
    J Exp Med. 1990 Dec 1;172(6):1777-84 PMID: 2258706
  11. Growth stimulation of human breast cancer cells with anti-transforming growth factor beta antibodies: evidence for negative autocrine regulation by transforming growth factor beta.
    Cell Growth Differ. 1990 Aug;1(8):367-74 PMID: 2177634
  12. Transforming growth factor beta 1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice.
    Cancer Res. 1991 Jul 1;51(13):3590-4 PMID: 2054795
  13. TGF-beta 1 is an autocrine-negative growth regulator of human colon carcinoma FET cells in vivo as revealed by transfection of an antisense expression vector.
    J Cell Biol. 1992 Jan;116(1):187-96 PMID: 1730743
  14. Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro.
    Mol Endocrinol. 1992 Jan;6(1):15-25 PMID: 1738367
  15. Transforming growth factor beta 1 in ductal carcinoma in situ and invasive carcinomas of the breast.
    Eur J Cancer. 1992;28(2-3):641-4 PMID: 1317202
  16. Altered metabolic and adhesive properties and increased tumorigenesis associated with increased expression of transforming growth factor beta 1.
    J Cell Biol. 1992 Aug;118(3):715-26 PMID: 1639853
  17. Transforming growth factor beta 1 can induce estrogen-independent tumorigenicity of human breast cancer cells in athymic mice.
    Cell Growth Differ. 1993 Mar;4(3):193-201 PMID: 8466857
  18. Factor VII related antigen as an endothelial cell marker in benign and malignant diseases.
    Virchows Arch A Pathol Anat Histol. 1981;391(2):217-25 PMID: 6784337
  19. Transforming growth factor production by chemically transformed cells.
    Cancer Res. 1981 Jul;41(7):2842-8 PMID: 6265069
  20. New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues.
    Proc Natl Acad Sci U S A. 1981 Sep;78(9):5339-43 PMID: 6975480
  21. Effects of orally administered retinol on natural killer cell activity in wild type BALB/c and congenitally athymic BALB/c mice.
    Cancer Immunol Immunother. 1986;21(2):114-8 PMID: 3633213
  22. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
    J Immunol. 1986 May 15;136(10):3916-20 PMID: 2871107
  23. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
    J Exp Med. 1986 May 1;163(5):1037-50 PMID: 2871125
  24. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.
    Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167-71 PMID: 2424019
  25. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes.
    J Immunol. 1986 Dec 15;137(12):3855-60 PMID: 2878044
  26. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.
    J Exp Med. 1987 Jan 1;165(1):251-6 PMID: 3491869
  27. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells.
    Cell. 1987 Feb 13;48(3):417-28 PMID: 2879636
  28. Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene.
    Proc Natl Acad Sci U S A. 1987 Feb;84(3):837-41 PMID: 2880347
  29. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta.
    EMBO J. 1987 Jun;6(6):1633-6 PMID: 3497030
  30. Effect of v-rasH oncogene transfection on estrogen-independent tumorigenicity of estrogen-dependent human breast cancer cells.
    Cancer Res. 1987 Nov 1;47(21):5733-8 PMID: 3664477
  31. Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family.
    EMBO J. 1987 Dec 1;6(12):3673-7 PMID: 3322813
  32. Regulation of the synthesis and activity of urokinase plasminogen activator in A549 human lung carcinoma cells by transforming growth factor-beta.
    J Cell Biol. 1988 Feb;106(2):451-9 PMID: 3276718
  33. Transforming growth factor beta: potential autocrine growth inhibitor of estrogen receptor-negative human breast cancer cells.
    Cancer Res. 1988 Jul 15;48(14):3898-904 PMID: 3164252
  34. Deactivation of macrophages by transforming growth factor-beta.
    Nature. 1988 Jul 21;334(6179):260-2 PMID: 3041283
  35. Transforming growth factor-beta: possible roles in carcinogenesis.
    Br J Cancer. 1988 Jun;57(6):594-600 PMID: 3044431
  36. The glioblastoma-derived T-cell suppressor factor/transforming growth factor beta 2 inhibits the generation of lymphokine-activated killer (LAK) cells.
    Int J Cancer. 1988 Oct 15;42(4):562-7 PMID: 3262591
  37. Transforming growth factors type beta 1 and beta 2 are equipotent growth inhibitors of human breast cancer cell lines.
    J Cell Physiol. 1989 Nov;141(2):353-61 PMID: 2808542
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI116871
Published
1993-12-00
Pages
2569-76
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC288452
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI116871 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: [email protected]

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