Vascular Endothelial Growth Factor and Its Relationship to Inflammatory Mediators

Abstract

Inflammation occurs in response to host injury or infection, as the result of an autoimmune disease, or in response to the development of a tumor. Although the immune system may be helpful in fighting the tumor, it may also fuel the tumorigenic process. In fact, recent data suggest a strong link between chronic inflammation, angiogenesis, and the development of cancer. For example, inflammation and scarring caused by recurring infections with Mycobacterium tuberculosis may be a cause for cancers of the lung. Inflammatory breast cancer exhibits increased angiogenesis and lymphangiogenesis and has a higher metastatic potential than noninflammatory breast cancer. Nonsteroidal anti-inflammatory drugs have been proposed as preventives for the development of colon carcinoma and ovarian cancer. Inhibition of nuclear factor-nB contributes to the proposed mechanism of action. Inflammatory cytokines, including interleukin-6, serve as autocrine and paracrine growth factors for several cancers, and high levels of these cytokines may correlate with a poor prognosis and increased production of angiogenic factors. The state of the art of our understanding of this critical interaction is reviewed.

The Role of Cytokines in Breast Cancer Development and Progression

“…Chronic inflammation can also lead to angiogenesis, because tumor-infiltrating lymphocytes secrete copious amounts of proinflammatory cytokines, such as IL-6, IL-1a, IL-1b, tumor necrosis factor-a, and oncostatin M, which are believed to upregulate COX-2, which, in turn, increases VEGF expression in tumor cells, promoting angiogenesis (Angelo and Kurzrock 2007). Inflammatory events can also lead to breast cancer metastasis.…”

Role of Inflammation and Angiogenic Growth Factors in Malignant Mesothelioma

“…In this context, the cross-talk between inflammation and angiogenesis is further corroborated by the evidence that, if on one hand inflammatory mediators have significant effects on angiogenesis, on the other hand angiogenic factors can effectively promote inflammation. As a matter of fact, in addition to their angiogenic role, VEGF and PlGF appear to act as direct proinflammatory mediators in the pathogenesis of different inflammatory conditions (Angelo & Kurzrock, 2007;Yoo et al, 2008). In this regard, VEGF was found to increase the production of TNF-and IL-6 by human peripheral blood mononuclear cells and macrophages (Yoo et al, 2008).…”

“…Cancer cells cocultured with macrophages and incubated with inflammatory cytokines are synergistically stimulated to produce various angiogenesis-related factors (Izzi et al, 2009;Ono, 2008). This inflammatory angiogenesis is mediated, in part, by activation of NF-κB and AP-1 (Angelo & Kurzrock, 2007;Huang et al, 2000;Ono, 2008). In fact, treatment of both vascular endothelial cells and cancer cells with IL-1 / , TNF-and ROS in vitro results in a marked induction of VEGF and FGF-2, through the transcriptional activation of NF-κB, Specificity protein 1 (Sp-1), AP-1 and hypoxia response elements.…”

“…In addition to macrophages, other tumor-infiltrating immune cells including T cells, B cells, natural killer cells and neutrophils can release cytokines, such as IL-1 / , TNF-and IL-6, able to sustain the synthesis of angiogenic growth factors (Angelo & Kurzrock, 2007). As for, IL-6, this pro-inflammatory cytokine has been reported to play a critical role in the stimulation of VEGF synthesis by different cell types, including MM cells (Adachi et al, 2006;Angelo & Kurzrock, 2007).…”

“…As for, IL-6, this pro-inflammatory cytokine has been reported to play a critical role in the stimulation of VEGF synthesis by different cell types, including MM cells (Adachi et al, 2006;Angelo & Kurzrock, 2007). Of note, MMs usually produce high levels of IL-6 but express low levels of IL-6R, so that the presence of sIL-6Rs, which may be provided by inflammatory cells recruited to the tumor region, is essential for the IL-6-dependent stimulation of VEGF expression by MM cells (Adachi et al, 2006).…”