Article

Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma.

Centre Pluridisciplinaire d'Oncologie, School of Medicine, University of Lausanne, Centre Hospitalier Universitaire Vaudois, Switzerland.
Nature Medicine (Impact Factor: 22.86). 04/1998; 4(4):408-14.
Source: PubMed

ABSTRACT Administration of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) to melanoma patients causes selective disruption of the tumor vasculature but the mechanism of this disruption is unknown. Here we report that exposure of human endothelial cells to TNF and IFN-gamma results in a reduced activation of integrin alphaVbeta3, an adhesion receptor that plays a key role in tumor angiogenesis, leading to a decreased alphaVbeta3-dependent endothelial cell adhesion and survival. Detachment and apoptosis of angiogenic endothelial cells was demonstrated in vivo in melanoma metastases of patients treated with TNF and IFN-gamma. These results implicate integrin alphaVbeta3 in the anti-vascular activity of TNF and IFN-gamma and demonstrate a new mechanism by which cytokines control cell adhesion.

0 Bookmarks
 · 
47 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thalidomide has reemerged as a promising anticancer and anti-inflammatory drug despite its devastating congenital birth defects. Many thalidomide derivatives with enhanced antiangiogenic and immunomodulatory effects or greater cytokine inhibition accompanied by less adverse toxicities than the parent drug have been developed. The mechanisms of action of thalidomide and its analogs are complex and not yet fully understood, but studies indicate that their antiangiogenic and immunomodulatory effects play important roles. Thalidomide and lenalidomide have been approved for the treatment of multiple myeloma and myelodysplastic syndrome. The powerful antiangiogenic, anti-inflammatory, and apoptotic effects mean that thalidomide and its immunomodulatory derivatives will continue to be explored in the treatment of a variety of cancers and inflammatory diseases.
    Tzu Chi Medical Journal 01/2008; 20(3):188-195.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis is an important process in normal physiology and disease pathogenesis. Angiogenesis is controlled in a healthy body by a system of angiogenic growth factors and angiogenesis inhibitors. When angiogenic growth factors are predominantly expressed, blood vessel growth occurs and disease may result. Successful therapies have been developed that target growth factors, their receptors, or the cascade pathways that are activated by growth factor/receptor interactions. There is good evidence that angiogenesis plays an important role in a wide range of cutaneous maladies, and angiogenesis-targeting therapies are playing an increasing role in the management of dermatologic disease. Cutaneous angiogenesis offers an exciting new arena for targeted dermatologic therapeutics. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to distinguish angiogenic growth factors and inhibitors, recognize angiogenic mediating agents and compare their mechanisms of action, and apply the use of angiogenic mediating agents in clinical and research situations.
    Journal of the American Academy of Dermatology 12/2009; 61(6):921-42; quiz 943-4. · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The connection between inflammation and tumorigenesis has been well established, based on a great deal of supporting evidence obtained from epidemiological, pharmacological, and genetic studies. One representative example is inflammatory bowel disease, because it is an important risk factor for the development of colon cancer. Moreover, intratumoral infiltration of inflammatory cells suggests the involvement of inflammatory responses also in other forms of sporadic as well as heritable colon cancer. Inflammatory responses and tumorigenesis activate similar sets of transcription factors such as NF-kB, Stat3, and hypoxia inducible factor and eventually enhances the expression of inflammatory cytokines including tumor necrosis factor (TNF) and chemokines. The expression of TNF and chemokines is aberrantly expressed in a mouse model of colitis-associated carcinogenesis as well as in inflammatory bowel disease and colon cancer in humans. Here, after summarizing the presumed actions of TNF and chemokines in tumor biology, we will discuss the potential roles of TNF and chemokines in chronic inflammation-associated colon cancer in mice.
    Cancers. 01/2011; 3(3):2811-26.