Effect of interleukin-8 on production of tumor-associated substances and autocrine growth of human liver and pancreatic cancer cells.
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.
Miyamoto
M
M
The Third Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama City, Japan.
Shimizu
Y
Y
Okada
K
K
Kashii
Y
Y
Higuchi
K
K
Watanabe
A
A
D015703:Antigens, CD / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000473:pathology; D019707:Receptors, Chemokine / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D015703:Antigens, CD; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins