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.
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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.
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Galunisertib is a well-studied small molecule inhibitor of TGF-β receptor kinases.
“One class, exemplified by galunisertib (LY2157299; developed by Eli Lilly) as a well-studied therapeutic291,292 consists of small molecule inhibitors of TGF-β receptor kinases.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [291]
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- Authors
- Arteaga, C. L., Hurd, S. D., Winnier, A. R., Johnson, M. D., Fendly, B. M., & Forbes, J. T.
- Affiliations
- Vanderbilt University (US)
- ORCID
- Arteaga, C L
- Venue
- Journal of Clinical Investigation
- Published
- 1993-12-01
- Volume
- 92
- Issue
- 6
- Pages
- 2569-2576
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288452
- OpenAlex
- W2146839556
- Cited by
- 359
- References
- 40
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 11 · 2012: 8
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- TGF-beta, anti-TGF-beta antibody, breast cancer, natural killer cells, tumor immunosuppression, tumor progression, metastasis, MDA-MB-231 cells, tumor microenvironment, host immune surveillance, tumor-host interaction
- MeSH terms
- Animals, Antibodies, Breast Neoplasms, Cell Division, Collagen, Cytotoxicity, Immunologic, Factor VIII, Female, Humans, Immunoglobulin G, Killer Cells, Natural, Lung Neoplasms, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Neovascularization, Pathologic, Recombinant Proteins, Spleen, Transplantation, Heterologous, Tumor Cells, Cultured, Transforming Growth Factor beta, Mice
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