Angiogenesis Links Chronic Inflammation with Cancer

  • Hanako Kobayashi
  • P. Charles Lin
Part of the Methods in Molecular Biology™ book series (MIMB, volume 511)


Angiogenesis, the formation of new blood vessels from existing vessels, is tightly linked to chronic inflammation and cancer. Angiogenesis is one of the molecular events bridging the gap between inflammation and cancer. One of the events linking inflammation and cancer is an increase in cellular adhesion molecules that are expressed on the luminal surface of endothelium upon inflammation. Cellular adhesion molecules are involved in leukocyte recruitment and subsequently lead to extravasation of leukocytes to the injury site. These adhesion molecules are known to be shared by some cancer cells and have the ability to contribute to metastasis. Thus, an elevation of these molecules in chronic inflammation may be a risk factor for metastasis. In this chapter, we discuss the method used to determine the adhesion molecules expressed on endothelium, and leukocyte adhesion to endothelium.

Key words

Angiogenesis Inflammation Leukocyte Adhesion ICAM-1 VCAM-1 E-selectin Metastasis HUVEC 


  1. 1.
    Folkman, J., and Shing, Y. (1992) Angiogen-esis. J Biol Chem 267, 10931–10934PubMedGoogle Scholar
  2. 2.
    Voronov, E., Shouval, D. S., Krelin, Y., Cagnano, E., Benharroch, D., Iwakura, Y., Dinarello, C. A., and Apte, R. N. (2003) IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 100, 2645–2650CrossRefPubMedGoogle Scholar
  3. 3.
    Costa, C., Incio, J., and Soares, R. (2007) Angiogenesis and chronic inflammation: cause or consequence? Angiogenesis 10, 149–166CrossRefPubMedGoogle Scholar
  4. 4.
    Esposito, I., Menicagli, M., Funel, N., Bergmann, F., Boggi, U., Mosca, F., Bevilacqua, G., and Campani, D. (2004) Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adeno-carcinoma. J Clin Pathol 57, 630–636CrossRefPubMedGoogle Scholar
  5. 5.
    Baron, J. A., and Sandler, R. S. (2000) Non-steroidal anti-inflammatory drugs and cancer prevention. Annu Rev Med 51, 511–523CrossRefPubMedGoogle Scholar
  6. 6.
    Thun, M. J., Namboodiri, M. M., and Heath, C. W., Jr. (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325, 1593–1596CrossRefPubMedGoogle Scholar
  7. 7.
    Masferrer, J. L., Leahy, K. M., Koki, A. T., Zweifel, B. S., Settle, S. L., Woerner, B. M., Edwards, D. A., Flickinger, A. G., Moore, R. J., and Seibert, K. (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60, 1306–1311PubMedGoogle Scholar
  8. 8.
    Dermond, O., and Ruegg, C. (2001) Inhibition of tumor angiogenesis by non-steroidal anti-inflammatory drugs: emerging mechanisms and therapeutic perspectives. Drug Resist Updat 4, 314–321CrossRefPubMedGoogle Scholar
  9. 9.
    Van der Auwera, I., Van Laere, S. J., Van den Eynden, G. G., Benoy, I., van Dam, P., Colpaert, C. G., Fox, S. B., Turley, H., Harris, A. L., Van Marck, E. A., Vermeulen, P. B., and Dirix, L. Y. (2004) Increased angiogenesis and lymphangio-genesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification. Clin Cancer Res 10, 7965–7971CrossRefPubMedGoogle Scholar
  10. 10.
    Huang, S., Robinson, J. B., Deguzman, A., Bucana, C. D., and Fidler, I. J. (2000) Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8. Cancer Res 60, 5334–5339PubMedGoogle Scholar
  11. 11.
    Kimba, Y., Abe, T., Wu, J. L., Inoue, R., Fukiki, M., Kohno, K., and Kobayashi, H. (2005) Mutant IkappaBalpha suppresses hypoxia-induced VEGF expression through downregula-tion of HIF-1alpha and COX-2 in human glioma cells. Oncol Res 15, 139–149PubMedGoogle Scholar
  12. 12.
    Ebnet, K., and Vestweber, D. (1999) Molecular mechanisms that control leukocyte extravasation: the selectins and the chemok-ines. Histochem Cell Biol 112, 1–23CrossRefPubMedGoogle Scholar
  13. 13.
    Kobayashi, H., Boelte, K. C., and Lin, P. C. (2007) Endothelial cell adhesion molecules and cancer progression. Curr Med Chem 14, 377–386CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Hanako Kobayashi
    • 1
  • P. Charles Lin
    • 1
  1. 1.Department of Radiation OncologyVanderbilt University Medical CenterNashvilleUSA

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