A Li1, M L Varney, R K Singh. 1. Department of Pathology and Microbiology, University of Nebraska Medical Center, 987660 Nebraska Medical Center, Omaha, NE 68198-7660, USA.
Abstract
PURPOSE: In the present study, we examined the expression of a multifunctional cytokine, interleukin 8 (IL-8), and its receptors, CXCR1 and CXCR2, in human colon carcinoma cells with different metastatic potentials and determined their role in modulating phenotypes associated with metastasis. EXPERIMENTAL DESIGN: IL-8, CXCR1, and CXCR2 protein and mRNA expression were examined using ELISA, immunocytochemistry, and reverse transcription-PCR in human colon carcinoma cells with different metastatic potentials. IL-8-mediated proliferation, migration, and tumor-endothelial cell interaction were analyzed. RESULTS: IL-8 mRNA and protein expression was very low in Caco2 cells but elevated in KM12C cells and very high in KM12L4 cells, suggesting an association between the IL-8 production and metastatic potential. Similarly, CXCR1 and CXCR2 expression was lower in Caco2 cells than in low and high metastatic KM12C and KM12L4 cells. The recombinant human IL-8 enhanced the proliferation of colon carcinoma cells. Furthermore, proliferation of low and high metastatic cells expressing different levels of IL-8 was inhibited by neutralizing antibodies to IL-8, CXCR1, and CXCR2. We observed significant differences in the invasive potential of colon carcinoma cells expressing different levels of IL-8. In addition, we observed that IL-8 modulates adhesion of tumor cells to endothelial cells in an autocrine and paracrine manner. CONCLUSION: Our present data suggest an association between constitutive expression of IL-8 and aggressiveness in human colon carcinoma cells and the possible role of IL-8 in modulating different metastatic phenotypes associated with progression and metastasis.
PURPOSE: In the present study, we examined the expression of a multifunctional cytokine, interleukin 8 (IL-8), and its receptors, CXCR1 and CXCR2, in humancolon carcinoma cells with different metastatic potentials and determined their role in modulating phenotypes associated with metastasis. EXPERIMENTAL DESIGN:IL-8, CXCR1, and CXCR2 protein and mRNA expression were examined using ELISA, immunocytochemistry, and reverse transcription-PCR in humancolon carcinoma cells with different metastatic potentials. IL-8-mediated proliferation, migration, and tumor-endothelial cell interaction were analyzed. RESULTS:IL-8 mRNA and protein expression was very low in Caco2 cells but elevated in KM12C cells and very high in KM12L4 cells, suggesting an association between the IL-8 production and metastatic potential. Similarly, CXCR1 and CXCR2 expression was lower in Caco2 cells than in low and high metastatic KM12C and KM12L4 cells. The recombinant humanIL-8 enhanced the proliferation of colon carcinoma cells. Furthermore, proliferation of low and high metastatic cells expressing different levels of IL-8 was inhibited by neutralizing antibodies to IL-8, CXCR1, and CXCR2. We observed significant differences in the invasive potential of colon carcinoma cells expressing different levels of IL-8. In addition, we observed that IL-8 modulates adhesion of tumor cells to endothelial cells in an autocrine and paracrine manner. CONCLUSION: Our present data suggest an association between constitutive expression of IL-8 and aggressiveness in humancolon carcinoma cells and the possible role of IL-8 in modulating different metastatic phenotypes associated with progression and metastasis.
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