Secretion of vascular endothelial growth factor from undifferentiated human thyroid carcinoma cell line (ACT-1)

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Proliferation and metastasis of undifferentiated human thyroid carcinoma cell line (ACT-1) was studied. The doubling time of ACT-1 was 48 hours. Transplantation of ACT-1 (2.5 x 10ィイD15ィエD1 cells) into subcutaneous tissues of severe combined immunodeficient (SCID) mice resulted in growing tumor, and pulmonary metastasis occurred three months after transplantation. Moreover, 3.0 x 10ィイD15ィエD1 cells of ACT-1 formed lung nodules three months after injection into the tail vein of SCID mice.ACT-1 cells secreted IL-6, IL-8, M-CSF, GM-CSF and vascular endothelial growth factor (VEGF) in high concentration into culture medium. Expression of VEGF mRNA in ACT-1 was confirmed by RT-PCR. Expression of VEGF protein in surgically resected tissue from the patient from whom ACT-1 was derived was also confirmed by immunohistochemical method.The effect of IL-6 and IL-8 on VEGF secretion from ACT-1 was studied. IL-8 did not make any influence on secretion of VEGF. However, IL-6 (100 ng/ml) stimulated secretion of VEGF from ACT-1, and this effect of IL-6 on VEGF secretion was neutralized by anti IL-6 antibody. Therefore, IL-6 produced by ACT-1 itself seems to stimulate the secretion from ACT-1 of VEGF, which develops the host vessels to support growth of carcinoma.