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Keratinocyte chemoattractant (KC)/human growth-regulated oncogene (GRO) chemokines and pro-inflammatory chemokine networks in mouse and human ovarian epithelial cancer cells.

Son DS, Parl AK, Rice VM, Khabele D
Cancer Biol Ther. 2007 6 (8): 1302-12

PMID: 17712227 · DOI:10.4161/cbt.6.8.4506

Chronic inflammation is an important underlying condition for ovarian tumor development, growth and progression. Since chemokine networks are activated by inflammation, patterns of chemokine gene expression were investigated in ovarian cancer cells. Chemokine specific microarrays were performed after mouse (ID8) and human (SKOV-3) ovarian surface epithelial cancer cells were exposed to the inflammatory agent bacterial endotoxin lipopolysaccharide (LPS, 10 microg/ml) and pro-inflammatory cytokines interleukin-1beta (IL-1, 10 ng/ml) and tumor necrosis factor-alpha (TNF, 10 ng/ml). In the mouse ID8 cells, LPS, IL-1 and TNF led to robust upregulation of keratinocyte chemoattractant (KC) chemokines CXCL1/2, mouse homologues of human growth-regulated oncogenes (GRO). Other chemokines, interferong inducible protein (IP)-10 (CXCL10), CCL7 and CCL20 were moderately upregulated. ID8 cells constitutively expressed CXCL16 and CCL2, but only CCL2 expression was enhanced by LPS, IL-1 and TNF. In the human SKOV-3 cells, LPS had no effect on chemokines expression due to the absence of the LPS receptor, toll-like receptor 4 (TLR4). However, IL-1 and TNF induced GROalpha/beta (CXCL1/2) in human SKOV-3 cells in a similar manner as observed with mouse ID8 cells. In SKOV-3 cells, IL-8 (CXCL8) was highly expressed and other chemokines GROgamma (CXCL3) and CCL20 were moderately expressed in response to IL-1 and TNF. The nuclear factor-kappaB (NF-kappaB) is a known mediator of cytokine and chemokines signaling. The NFkappaB inhibitor BAY 11-7082 attenuated expression of inflammatory-induced chemokines in the mouse and human ovarian cancer cells. Taken together, the results indicate that KC/GRO chemokines are the principal chemokines induced by LPS and pro-inflammatory cytokines IL-1 and TNF via NFkappaB signaling in ovarian surface epithelial cancer cells.

MeSH Terms (15)

Animals Carcinoma Chemokine CXCL1 Chemokines Chemotactic Factors Female Humans Interleukin-1 Lipopolysaccharides Mice NF-kappa B Oligonucleotide Array Sequence Analysis Ovarian Neoplasms Signal Transduction Tumor Necrosis Factor-alpha

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