Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis.

By Li Yang, Jianhua Huang, X. Ren, Agnieszka E. Gorska, A. Chytil, M. Aakre, D. Carbone, L. Matrisian, A. Richmond, P. Lin and 1 more. Cancer Cell, 2008

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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.

Subfields: Cancer Research, Immunology and Allergy, Oncology

View Paper: https://www.semanticscholar.org/paper/7b3f7f44ce4267abf6a8d286578e12ebfc33c82e

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Citations in the corpus

TGFβ in Cancer (2008, background): “The presence of these tumor-infiltrating cells coincides with TGFβ secretion and is thus a suspected source of the accumulation of TGFβ1 at the invasion front of the tumor (Yang et al., 2008).”
The role of myeloid cells in the promotion of tumour angiogenesis (2008, background): “MDSC have also been detected in experimental murine tumour”
The metastatic niche: adapting the foreign soil (2009, background): “In studies of the primary tumour, other groups have distinguished between GR1 + MAC1 + immature myeloid cells (also known as myeloid-derived suppressor cells (MDSCs)) and terminally differentiated, MAC1 + F4/80 + tumour-associated macrophage”
Dual Roles of Immune Cells and Their Factors in Cancer Development and Progression (2011, background): “18) , and may also serve to promote tumor development and immunoregulation with M2-like TAM inhibiting anti-cancer immunity through the production of transforming growth factor β1 (TGF-β) and IL-10 (14, 18, 19).”
The nature of myeloid-derived suppressor cells in the tumor microenvironment (2016, neutral): “CXCL5 Mammary carcinoma (mouse) MDSC [103]”
CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages (2009, methodology): “Yang and colleagues recently reported that CD11bGr1 IMCs are recruited into mammary carcinomas and regulate pulmonary metastasis in PyMT mice via activation of TGF-bregulated signaling pathways (Yang et al., 2008).”
Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy (2014, background): “(33) showed that Gr1CD11b MDSCs are recruited into murine mammary carcinomas via a CXCR2-dependent mechanism and, once there, act to promote tumor invasion and metastasis.”
Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer (2009, background): “The nonimmune mechanisms include the following: 1) the production of reactive oxygen species (ROS)(3) such as peroxynitrites, which cause DNA mutations that contribute to genetic instability and the proliferation of malignant cells (2); 2) the production of proangiogenic factors such as vascular end”