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


METHODS
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.


CONCLUSIONS
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.
Li
A
A
Department of Pathology and Microbiology, University of Nebraska Medical Center, 987660 Nebraska Medical Center, Omaha, NE 68198-7660, USA.
Varney
M L
ML
Singh
R K
RK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B