Effect of interleukin-8 on production of tumor-associated substances and autocrine growth of human liver and pancreatic cancer cells

Abstract

We have previously reported that human liver cancer cell lines produce interleukin-8 (IL-8) at high levels. Those tumor cells appeared to express two kinds of IL-8 receptor on their surface. In order to analyze the role of IL-8 on the biological characteristics of those tumor cells, we suppressed IL-8 production from human liver (HuH-7 and HuCC-T1) and pancreatic cancer cell lines (HuP-T4) by treatment with IL-8 antisense oligonucleotides. Suppression of IL-8 production resulted not only in inhibition of cell growth, but also in an increase in the concentrations of some tumor-associated substances such as carbohydrate antigen 19-9 (CA19-9) in the medium. These data indicate that IL-8 produced by human liver and pancreatic tumors may act as an autocrine growth factor and may control the production of some tumor-associated substances. Furthermore, surface expression of sialyl-Lewis(a), which is a ligand for ELAM-1 on human umbilical vein endothelial cells (HUVEC), HuCC-T1 and HuP-T4 cells was decreased and the attachment of these tumor cells to HUVEC was inhibited by treatment with IL-8 antisense oligonucleotide. Since the soluble form of CA19-9 (sialyl-Lewis(a)) was shown to inhibit the tumor cell binding to HUVEC, the decrease in release of CA19-9 into the medium and increase in the expression of sialyl-Lewis(a) on the cell surface may suggest that IL-8 production from the tumor cells enhances metastatic potential by augmenting the binding activity of the tumor cells to HUVEC. These data demonstrate that a cytokine produced by tumor cells may function as an autocrine growth factor and affect tumor cell dissemination.

Interleukin-8/CXCL8 is a growth factor for human lung cancer cells

“…Interleukin-8 has been shown to be an important mitogenic factor in a variety of cancers including melanoma (Schadendorf et al, 1993;Singh et al, 1994), colon cancer (Brew et al, 2000;Li et al, 2001), pancreatic cancer (Miyamoto et al, 1998), malignant mesothelioma (Galffy et al, 1999) and Kaposi's sarcoma (Masood et al, 2001). The role of IL-8 in lung cancer has not been fully defined.…”

“…Elevated IL-8 is correlated with angiogenesis, tumour progression and poor survival in NSCLC (Yuan et al, 2000;Masuya et al, 2001;Orditura et al, 2002;Chen et al, 2003). CXCL8 has been shown to be mitogenic for cancers such as melanoma (Schadendorf et al, 1993), colon cancer (Brew et al, 2000;Li et al, 2001), pancreatic cancer (Miyamoto et al, 1998), malignant mesothelioma (Galffy et al, 1999) and Kaposi's sarcoma (Masood et al, 2001). However, the role of IL-8 in lung cancer has been controversial.…”

Inhibitory effects of cyclosporin A on calcium mobilization-dependent interleukin-8 expression and invasive potential of human glioblastoma U251MG cells

“…IL-8 has been shown to stimulate proliferation of a variety of cancer cells such as melanoma, pancreatic cancer and colon cancer cells (Schadendorf et al, 1993;Miyamoto et al, 1998;Brew et al, 2000). However, the effect of IL-8 on glioma cell growth seems to be elusive.…”

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion

“…CXCL-8, a member of the CXC chemokine family, has been reported to induce migration, stimulate angiogenesis and promote tumour cell growth in melanoma and other malignancies (Matsushima and Oppenheim, 1989;Wang et al, 1990;Koch et al, 1992;Schadendorf et al, 1993;Youngs et al, 1997;Miyamoto et al, 1998;Bar-Eli, 1999;Singh and Varney, 2000;Li et al, 2002). CXCL-8 is a multifunctional cytokine/growth factor that binds to two high-affinity receptors: type A CXCL-8 receptor (IL-8RA/IL-8RI or CXCR1) and type B CXCL-8 receptor (IL-8RB/IL-8RII or CXCR2; Holmes et al, 1991;Murphy and Tiffany, 1991).…”