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

Research output: Contribution to journalArticle

310 Scopus citations

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
Publication statusPublished - Jan 1 1993

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Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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