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.
- Matsushima, K. et al. (1988) J. Exp. Med. 167:1883.
- Koch, A.E. et al. (1992) Science 258:1798.
- Strieter, R.M. et al. (1992) Am. J. Pathol. 141:1279.
- Wang, J.M. et al. (1990) Biochem. Biophys. Res. Commun.169:165.
- Singh, R.K. et al. (1994) Cancer Res. 54:3242.
- Singh, R.K. et al. (1995) Cancer Res. 55:3669.
- Schelbenbogen, C. et al. (1995) Melanoma Res. 5:179.
- Luca, M. et al. (1997) Am. J. Pathol. 151:1105.