Interleukin-6-mediated autocrine growth promotion in human glioblastoma multiforme cell line U87MG.
Human glioblastoma multiforme cell lines, brain tumor biopsy tissue, and normal human fetal brain synthesize interleukin (IL)-6 and IL-6 receptor (IL-6R). Neither of these is expressed in human neurons or neuroblastoma cell lines in culture. Astrocytes from fetal brain grown in culture retain the ability to synthesize IL-6 but do not express IL-6R as inferred from RT-PCR and Southern blot studies. Coexpression of IL-6 and IL-6R in the glioblastoma cell line U87MG is confirmed by immunofluorescence staining. Both specific monoclonal antibodies against IL-6 and IL-6R and antisense oligonucleotide to IL-6 mRNA inhibit the growth of U87MG cells in culture, suggesting the existence of a functional autocrine growth loop. Anti-IL-6 antibodies also inhibit the growth of glioblastoma cell lines U373 and U118. The expression of IL-6 by human fetal astrocytes in culture is highly suggestive of its role as an oncofetal protein responsible for rapid proliferation of fetal and tumor cells but not cells of adult brain.
Goswami
S
S
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi.
Gupta
A
A
Sharma
S K
SK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003470:Culture Media / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000906:Antibodies; D016375:Antisense Elements (Genetics); D003470:Culture Media; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6