Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials.

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.

• Authors: A Li, M L Varney, R K Singh
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 7 Issue 10 Pg. 3298-304 (Oct 2001) ISSN: 1078-0432 [Print] United States
• PMID: 11595728 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Interleukin-8
• RNA, Messenger
• Receptors, Interleukin-8A
• Receptors, Interleukin-8B

Topics

• Animals
• Antibodies (pharmacology)
• Caco-2 Cells
• Cell Adhesion (drug effects)
• Cell Division (drug effects)
• Cell Line
• Cell Movement (drug effects)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Dose-Response Relationship, Drug
• Endothelium, Vascular (cytology, drug effects)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Interleukin-8 (genetics, metabolism, pharmacology)
• Neoplasm Metastasis
• RNA, Messenger (genetics, metabolism)
• Receptors, Interleukin-8A (genetics, immunology, metabolism)
• Receptors, Interleukin-8B (genetics, immunology, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction