Chemokines in tumor-associated angiogenesis

Abstract

Tumor growth is dependent on several key factors. Apart from immune escape and an efficient blockade of apoptotic signals, tumors require oxygen and nutrients to grow past a diameter of 2 microm. Therefore, it is of vital importance for the tumor to facilitate tumor-associated angiogenesis, e.g., the de novo formation of new blood vessels. In addition to established and key angiogenic factors, such as vascular endothelial growth factor, chemokines, a superfamily of cytokine-like proteins that bind to seven transmembrane-spanning G-protein-coupled receptors, have been associated with angiogenesis under homeostatic conditions. Chemokines were initially identified as key factors that control the directional migration of leukocytes, stem cells and cancer cells in vitro and which critically regulate their trafficking in vivo. Recently their role in establishing a favorable microenvironment for tumor-associated angiogenesis, a process that requires complex bidirectional interactions of the tumor and associated vessels, has been the focus of research. Chemokine-promoted angiogenesis not only facilitates tumor growth by supplying nutrients and oxygen but it is also a prerequisite to tumor metastasis. Hence, the pharmacologic control of tumor angiogenesis presents a promising strategy for novel anticancer therapeutics. Here, we discuss the current pathogenetic concepts of tumor-associated angiogenesis in the context of chemokines and their receptors and highlight promising therapeutic strategies.

Association of chemokine and chemokine receptor expression with the invasion and metastasis of lung carcinoma

“…A previous study reported evidence of crosstalk between the IL-8 and epidermal growth factor receptor (EGFR); in addition, EGFR-induced Ras activation promoted the expression of CXCL8/IL-8 and CXCL1 in tumor cells (23). Therefore, these chemokines were found to promote tumor cell proliferation via autocrine loops and promote tumor-associated angiogenesis through CXCR2 in a paracrine manner (24). In the present study, CXCR2 mRNA expression levels, but not CXCR1, were found to be associated with a high incidence of lymph node metastasis and high TNM staging.…”

A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer

“…32,33 Thus, CAFs may orchestrate a distorted architecture of the host tissue and a functional "corrupted" stroma which in turn helps the metastatic spread. 34 Nevertheless, these CAFs are heterogeneous populations and their relative composition greatly differs among tumors. The origin of CAFs is matter of debate and many origins have been proposed, such as resident normal fibroblasts, derivation from mesenchymal stem cells or transdifferentiation of epithelial and endothelial cells.…”

Individual approach in choosing second-line targeted therapy for metastatic renal cell carcinoma

“…Действительно, некоторые авторы показали, что прогрессирование заболевания на фоне длитель-ной таргетной терапии связано в том числе с развити-ем лекарственной резистентности к препаратам, действующим через патогенетический путь, ассоции-рованный с HIF / VEGF. В механизме развития лекар-ственной резистентности играют роль непрерывная активация оси VEGF с помощью эффекторов восхо-дящего или нисходящего потока [33], активация VEGF-независимых путей, таких как bFGF, c-met, IL8 или других ангиогенных цитокинов [34] …”