IL-8 and Metastasis

Tumor cell metastasis is a complex, multi-step process. In order to metastasize, a tumor cell must be able to invade surrounding tissue, disseminate via the lymphatic system or bloodstream, extravasate and subsequently proliferate at a secondary location. Cytokines/growth factors play an important role in tumor cell metastasis by promoting, for example, tumor cell proliferation, adhesion, migration, proteolytic degradation of extracellular matrix components, and angiogenesis.

Interleukin 8 (IL-8), originally identified as a leukocyte chemoattractant,1 is involved in melanoma progression. IL-8 induces angiogenesis2-3 and haptotactic migration4 in melanoma cells, and increased expression of IL-8 in human melanoma cells correlates with their metastatic potential.5-6 In addition, serum IL-8 was elevated in patients with metastatic melanoma and was correlated with tumor load.7

Luca et al.8 demonstrated that expression of IL-8 in low-tumorigenic, nonmetastatic melanoma cells significantly increased their tumorigenicity and metastatic potential. The IL-8 transfected melanoma cells displayed an up-regulation in MMP-2 activity and mRNA levels and increased invasiveness compared to parental or control-transfected cells.8 IL-8 appears to increase metastatic potential specifically by inducing MMP-2 production, thus facilitating melanoma invasion of surrounding tissues.


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  2. Koch, A.E. et al. (1992) Science 258:1798.
  3. Strieter, R.M. et al. (1992) Am. J. Pathol. 141:1279.
  4. Wang, J.M. et al. (1990) Biochem. Biophys. Res. Commun.169:165.
  5. Singh, R.K. et al. (1994) Cancer Res. 54:3242.
  6. Singh, R.K. et al. (1995) Cancer Res. 55:3669.
  7. Schelbenbogen, C. et al. (1995) Melanoma Res. 5:179.
  8. Luca, M. et al. (1997) Am. J. Pathol. 151:1105.