Human carcinoma cells express IL-8 and IL-8 receptor: their role and regulation in cancer biology

It has been reported that a large number of carcinoma cells are able to produce a variety of cytokines. We also reported that many carcinoma cell lines constitutively produce IL-8 in supernatant cultures. To evaluate the in vivo function of IL-8 of carcinoma cells, we investigated the expression of IL-8 and IL-8 receptors (IL-8R) in human carcinoma cells and the role of IL-8 and IL-8R in the growth of carcinoma cells. IL-8 mRNA was detected in 16 out of 20 (80%) carcinoma cell lines and 20 out of 24 (83.3%) carcinoma tissues by Northern blot analysis. IL-8R mRNA was expressed in 7 out of 11 (63.6%) carcinoma cell lines by reverse transcriptase–polymerase chain reaction (RT-PCR). Neutrophil chemotactic activity in supernatant cultures of carcinoma cell lines correlated with immunoreactive IL-8 concentration. Growth of carcinoma cells was significantly inhibited in the presence of anti-IL-8 antibodies or IL-8R antisense oligonucleotides. These results revealed that IL-8 and IL-8R are expressed in the majority of carcinoma cells, and it suggests that they might play a role in the growth of carcinoma cells.On the other hand, the NF-κB/Rel families are crucial transcriptional factors for regulation of IL-8 in immune and inflammatory responses. To determine if IL-8 production in carcinoma cells is associated with activation of nuclear factor κB (NF-κB), we investigated MCF-7 breast carcinoma cells with 12-O-teradecanoyl-phorbol-13-acetate (TPA) treatment. After TPA treatment, ELISA showed IL-8 production was increasing in culture supernatant. Western blotting revealed that in concert with the decline in cytosolic IκB, NF-κB exhibited similar kinetics of translocation to the nucleus. Electrophoric mobility shift assay (EMSA) also revealed that activation of NF-κB. These findings suggest that activation of NF-κB regulates IL-8 expression in carcinoma cells. [Copyright &y& Elsevier]