Abstract
Murine macrophage inflammatory protein-1 (MIP-1)α gene transfection into human oral squamous cell carcinoma cells (HSC3/MIP-1α) was examined for its effects on cell growth and cytokine mRNA expression. The human oral carcinoma cell line HSC3 was transfected separately with a control plasmid and an mu-MIP-1α expression vector. Immunocompetent BALB/c mice were inoculated into the back skin with the cells. Primary tumor growth and tumor immunogenicity were investigated, and morphological analyses were carried out. HSC3/MIP-1α cells synthesized relatively large amounts of MIP-1 protein, whereas the HSC3/vector mediated control did not synthesize MIP-1 protein or mRNA. Further, it was shown that the HSC3/MIP-1α culture supernatants showed chemo-attraction to macrophages. In vivo, the tumorigenicity of HSC3/MIP-1α was significantly reduced in BALB/c nu/nu mice when compared with vector transfection alone. In addition, histological examination showed that numerous MAC-1 positive cells were recruited to the HSC3/MIP-1α mediated tumor nests after 10 days, whereas no such activity was seen in the controls. These results indicate that liposome-mediated MIP-1α gene transfection is efficient for MIP-1α protein synthesis of tumor cells. Although the gene transient efficiency was available for only a limited period, MIP-1α gene transfection reduced tumor size. The present technique, which must still be further developed, may provide stable integration efficiency of a foreign gene for use in long-term gene expression.
