White blood cells play key roles in the body’s defense against disease-causing agents. One type of white blood cell, granulocytes, plays an important role in inflammation. It is known that inflammation influences cancer development and spread (metastasis). Neutrophils, the most abundant of the granulocytes, respond to messages released by tumor cells and affect the tumor growth process.
Neutrophils enhance tumor blood supplies by stimulating a process called angiogenesis. Angiogenesis is the formation of new blood vessels from existing ones. This process is a very crucial step in tumor development. Factors that regulate neutrophil production have been studied in mice. One of these factors is called granulocyte colony-stimulating factor (G-CSF). High levels of G-CSF have been found in mouse and human cancer tissue. Blocking G-CSF release from cells in mice curbs abnormal buildup of neutrophils and prevents the further development of the tumor blood supply.
In mice that lack an anti-tumor factor called IFN-beta, tumor blood supply increases, neutrophil levels go up, and the tumors grow more aggressively. When neutrophils are reduced in these mice, the enhanced angiogenesis and growth of tumors is halted. Vascular endothelial growth factor (VEGF) is a potent factor that promotes angiogenesis. Tumor-related neutrophils contain and can release large amounts of VEGF. Another neutrophil factor, MMP9, causes the release of VEGF and other tumor-promoting factors from neutrophils. For this reason, VEGF has been targeted as a form of cancer treatment.
However, resistance to anti-VEGF treatment has been observed. This occurs by a complex interaction of various factors that enter tumor cells and reduce the success of anti-VEGF therapy. The previously mentioned G-CSF produced by tumor cells enhances the accumulation of these factors.
The role of neutrophils in cancer is very complex. There is still much to be learned about this process and how it can be exploited to develop new cancer therapies. A goal then is to find out how to block the angiogenic and other pro-tumor effects of neutrophils while preserving the protective functions.
Liang, Wei and Napoleone Ferrara. "The Complex Role Of Neutrophils In Tumor Angiogenesis And Metastasis". Cancer Immunology Research 4.2 (2016): 83-91. Web. 17 Aug. 2016.