Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine.
Angiogenesis, a key rate-limiting step in the growth and dissemination of malignant tumors, is regulated by the balance between positive and negative effectors. Recent studies indicate that the pleiotropic cytokine interleukin-6 (IL-6) may contribute to the vascularization of some tumors by disrupting the equilibrium between positive and negative angiogenic regulatory molecules. We determined whether IL-6 participates in the angiogenesis observed during the progression of ovarian carcinoma. We measured IL-6 production by human ovarian cancer cell lines in vitro and in vivo. Not all cell lines secreted IL-6 in vitro; however, when the cell lines were implanted into the peritoneal cavity of female nude mice, every line secreted IL-6. Most human ovarian carcinoma cell lines tested secreted significant levels of the soluble IL-6 receptor (sIL-6R). Endothelial cell lines established from the ovary and mesentery of female H-2K(b)-tsA58 mice were tested for response to IL-6. Both endothelial cell lines expressed the IL-6R and their stimulation with the exogenous ligand significantly enhanced cell migration and activated the downstream signaling molecule signal transducers and activators of transcription 3. Dual immunohistochemical staining for IL-6R and CD31 revealed IL-6R expression on human endothelial cells within normal ovary and carcinoma specimens. Gelfoam sponges containing 0.4% agarose and IL-6 or basic fibroblast growth factor and implanted into the subcutis of BALB/c mice were vascularized to the same extent. Collectively, the data indicate that ovarian tumor cells secreted IL-6, a highly angiogenic cytokine that supports progression of disease.
Nilsson
Monique B
MB
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77230-1429, USA.
Langley
Robert R
RR
Fidler
Isaiah J
IJ
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D010053:Ovary / Q000098:blood supply; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor