Interleukin 8: an autocrine growth factor for human ovarian cancer.
We determined whether interleukin-8 (IL-8) plays a direct role in the progressive growth of ovarian cancer cells by isolating high- and low-IL-8-producing clones from the parental Hey-A8 human ovarian cancer cell line and compared their proliferative activity and tumorigenicity in nude mice. The effect of exogenous IL-8 and mouse antihuman IL-8 neutralizing antibody on ovarian cancer cell proliferation was investigated. Finally, we studied the modulation of IL-8 production in ovarian cancer cells by sense and antisense IL-8 expression vector transfection and its effect on proliferation. The Hey-A8(H) clone was selected for its overexpression of IL-8. It has a significantly higher proliferation rate than the low-IL-8-producing clone, Hey-A8(L). Recombinant IL-8 (50 ng/ml) caused a significant increase in proliferation of Hey-A8(L) clones, and 10 microg/ml neutralizing antibody against IL-8 significantly decreased proliferative activity of both Hey-A8(H) and Hey-A8(L) clones. Enforced IL-8 expression by IL-8 expression vector transfection in Hey-A8(L) clones significantly increased tumor cell proliferation, microvessel density, and hence, tumorigenicity. We conclude that IL-8 has a direct and indirect growth-potentiating activity in human ovarian cancer cells.
Xu
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Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Fidler
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D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D016209:Interleukin-8; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011994:Recombinant Proteins