CXC and CC chemokines as angiogenic modulators in nonhaematological tumors

Abstract

Chemokines are a superfamily of structurally homologous heparin-binding proteins that includes potent inducers and inhibitors of angiogenesis. The imbalance between angiogenic and angiostatic chemokine activities can lead to abnormalities, such as chronic inflammation, dysplastic transformation, and even tumor development and spreading. In this review, we summarize the current literature regarding the role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in patients with nonhaematological tumors.

Figure 1

The role of CXCL8 signaling in the tumor microenvironment. Autocrine CXCL8 production by cancer cells can enhance their proliferation and survival of cancer cells through autocrine signaling pathways. Tumor-derived CXCL8 promotes angiogenesis, cell invasion, and migration. In addition, CXCL8 induces a chemotactic infiltration of neutrophils into the tumor site and the secretion of additional growth factors by tumor-associated macrophages.

Figure 2

The transcription factor TWIST1 promotes angiogenesis and tumor progression without increasing the secretion of VEGF but rather by inducing the expression of the macrophage chemoattractant CCL2. Tumor cells that express Twist1 upregulate CCL2 transcript, increase CCL2 protein levels, and lead to the formation of a CCL2 gradient in tumor microenvironment. This gradient attracts macrophages, which promote tumor angiogenesis.