Cited by 925TGF-β signaling in diseasesImmune cells in cancerChemokine receptors and signaling

Abrogation of TGFβ Signaling in Mammary Carcinomas Recruits Gr-1+CD11b+ Myeloid Cells that Promote Metastasis

Open access
Yang, Li, Huang, Jianhua, Ren, Xiubao, Gorska, Agnieszka E., Chytil, Anna, Aakre, Mary, Carbone, David P., Matrisian, Lynn M. +3 more·2008·Cancer Cell

Abstract

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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Registry

Crossref · 10.1016/j.ccr.2007.12.004

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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.”
  • 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.
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2008-01
Volume
13
Issue
1
Pages
23-35
ISSN
1535-6108 (ISSN-L)
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
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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