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.
The Third Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama City, Japan.
M
M
Miyamoto
Y
Y
Shimizu
K
K
Okada
Y
Y
Kashii
K
K
Higuchi
A
A
Watanabe
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