Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis.

By Li Yang, L. Debusk, K. Fukuda, B. Fingleton, B. Green-Jarvis, Y. Shyr, L. Matrisian, D. Carbone, P. Lin. Cancer Cell, 2004

1,178 citations recorded by the source corpus.

We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. Gr+CD11b+ cells were also found to directly incorporate into tumor endothelium. Consistent with this observation, Gr+CD11b+ cells acquire endothelial cell (EC) properties in tumor microenvironment and proangiogenic culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs.

Subfields: Cancer Research, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/42c55b1179d50e37f9eb2608e937dd8f47ee1fa9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Zena Werb
2. T. Cox
3. J. Erler
4. A. Mantovani
5. A. Sica
6. L. Matrisian
7. R. DePinho
8. V. Bronte

In Immunology

1. A. Mantovani
2. A. Sica
3. S. Ostrand-Rosenberg
4. D. Gabrilovich
5. P. Allavena
6. V. Bronte
7. P. Sinha
8. C. Garlanda

In Molecular Biology

1. Zena Werb
2. A. Mantovani
3. D. Hanahan
4. P. Allavena
5. T. Cox
6. A. Sica
7. J. Erler
8. R. Weinberg

Citations in the corpus

• Myeloid derived suppressor cells (2013, background): “MDSCs are actively recruited to the tumor microenvironment, where they not only release factors that promote blood vessel formation, but they differentiate into CD31 cells that incorporate into the newly forming endothelium.(8) These infiltrating cells produce matrixmetalloproteinase-9 (MMP-9),(21) ”
• Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. (2006, background): “Recently, Gr-1Mac-1 immature myeloid cells have been shown to promote tumor angiogenesis by directly incorporating into the tumor endothelium and thus promote tumor development and growth (48).”
• Genetics and biology of prostate cancer (2018, background): “…play a major role in the suppression of immune responses in cancer through a variety of mechanisms (Gabrilovich and Nagaraj 2009), and have been implicated in the promotion of angiogenesis, tumor cell invasion, and metastases (Yang et al. 2004, 2008; Condamine et al. 2015; Kumar et al. 2016b).”
• Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the pre-metastatic niche (2009, background): “CD11b+Gr-1+ cells also incorporate into tumor endothelium and enhance angiogenesis (Yang et al., 2004), while CD11b+ myeloid cells enhance tumor growth through vasculogenesis (Ahn and Brown, 2008).”