Abrogation of TGFβ Signaling in Mammary Carcinomas Recruits Gr-1+CD11b+ Myeloid Cells that Promote Metastasis
Open accessAbstract
Aberrant TGFbeta signaling is common in human cancers and contributes to tumor metastasis. Here, we demonstrate that Gr-1+CD11b+ myeloid cells are recruited into mammary carcinomas with type II TGF beta receptor gene (Tgfbr2) deletion and directly promote tumor metastasis. Gr-1+CD11b+ cells infiltrate into the invasive front of tumor tissues and facilitate tumor cell invasion and metastasis through a process involving metalloproteinase activity. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGF beta 1 in tumors with Tgfbr2 deletion. The recruitment of Gr-1+CD11b+ cells into tumors with Tgfbr2 deletion involves two chemokine receptor axes, the SDF-1/CXCR4 and CXCL5/CXCR2 axes. Together, these data indicate that Gr-1+CD11b+ cells contribute to TGFbeta-mediated metastasis through enhancing tumor cell invasion and metastasis.
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Data from various mouse models indicate that disrupting the CXCR1/2-MDSC axis is therapeutically efficacious across a wide variety of solid cancers.
“Notably, data from various mouse models indicate that disrupting the CXCR1/2–MDSC axis in tumours is therapeutically efficacious across a wide variety of solid cancers166–172.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [172]
TGF-β suppresses antigen presentation by DCs, impairing T-cell-mediated anti-tumor responses, and may suppress DC migration.
“TGF-β suppresses antigen presentation by DCs, thus impairing T-cell-mediated anti-tumor responses183, and may suppress DC cell migration184,185.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [183]
TGF-β signaling suppresses processes that lead to CD8+ T cell activation and maturation, including, in APCs, expression of components of the antigen processing and presentation machinery, such as HLA/MHC.
“TGF-β signaling suppresses processes that lead to CD8+ T cell activation and maturation, including, in APCs, expression of components of the antigen processing and presentation machinery, such as HLA/MHC175,183,202.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [183]
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- Authors
- Yang, L., Huang, J., Ren, X., Gorska, A. E., Chytil, A., Aakre, M., Carbone, D. P., Matrisian, L. M., Richmond, A., Lin, P. C., & Moses, H. L.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Moses, Harold L.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 13
- Issue
- 1
- Pages
- 23-35
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2245859
- OpenAlex
- W2130870648
- Cited by
- 918
- References
- 61
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 30 · 2023: 25 · 2022: 41 · 2021: 58 · 2020: 41 · 2019: 52 · 2018: 42 · 2017: 47 · 2016: 62 · 2015: 59 · 2014: 64 · 2013: 78 · 2012: 77
- FWCI
- 29.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK6 BX005225)
- Vanderbilt University
- National Cancer Institute (CA068485, CA 085492, R01CA085492, R01CA116021, CA102162, R01CA108856, CA126505, R01CA076321, R01CA034590, P50CA098131, R01CA102162, CA108856, P30CA068485, U54CA126505)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK58404, P30DK058404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- TGF-beta signaling, breast cancer, tumor-associated macrophages, metastasis, tumor invasion, metalloproteinase activity, SDF-1/CXCR4 axis, chemokine receptors, myeloid cell recruitment
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type II, Animals, Breast Neoplasms, Female, Humans, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Signal Transduction, Transforming Growth Factor beta, Protein Serine-Threonine Kinases, Gene Deletion, Receptors, Transforming Growth Factor beta, Matrix Metalloproteinases, Myeloid Cells, CD11b Antigen, Cell Line, Tumor, Mice
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