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

C. L. Arteaga, S. D. Hurd, A. R. Winnier, M. D. Johnson, B. M. Fendly, J. T. Forbes

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Abstract

TGF-β 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-β1, -β2, and -β3, 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-β 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-β 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF- β in the progression of mammary carcinomas by suppressing host immune surveillance.

Original languageEnglish (US)
Pages (from-to)2569-2576
Number of pages8
JournalJournal of Clinical Investigation
Volume92
Issue number6
StatePublished - Jan 1 1993

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Transforming Growth Factors
Natural Killer Cells
Spleen
Breast Neoplasms
Antibodies
Neoplasms
Nude Mice
Neoplasm Metastasis
Serum-Free Culture Media
Conditioned Culture Medium
Intraperitoneal Injections
Human Activities
Immunoglobulin G
Lymphocytes
Cell Line
Lung
Growth

Keywords

  • breast neoplasms
  • immunologic surveillance
  • natural killer activity
  • nude mice
  • transforming growth factor-β

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{37ce297a4a75429c8ffc03f2a41b76af,
title = "Anti-transforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-β interactions in human breast cancer progression",
abstract = "TGF-β 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-β1, -β2, and -β3, 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-β 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-β 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF- β in the progression of mammary carcinomas by suppressing host immune surveillance.",
keywords = "breast neoplasms, immunologic surveillance, natural killer activity, nude mice, transforming growth factor-β",
author = "Arteaga, {C. L.} and Hurd, {S. D.} and Winnier, {A. R.} and Johnson, {M. D.} and Fendly, {B. M.} and Forbes, {J. T.}",
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T1 - Anti-transforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-β interactions in human breast cancer progression

AU - Arteaga, C. L.

AU - Hurd, S. D.

AU - Winnier, A. R.

AU - Johnson, M. D.

AU - Fendly, B. M.

AU - Forbes, J. T.

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N2 - TGF-β 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-β1, -β2, and -β3, 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-β 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-β 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF- β in the progression of mammary carcinomas by suppressing host immune surveillance.

AB - TGF-β 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-β1, -β2, and -β3, 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-β 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-β 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF- β in the progression of mammary carcinomas by suppressing host immune surveillance.

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