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VEGF secretion is inhibited by interferon-alpha in several melanoma cell lines.
- Source :
-
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research [J Interferon Cytokine Res] 2008 Sep; Vol. 28 (9), pp. 553-61. - Publication Year :
- 2008
-
Abstract
- Interferon-alpha (IFN-alpha) is employed in the treatment of malignant melanoma; however, it mediates regression of disease in only 10-15% of patients. Currently, its mechanism of action is uncharacterized. Low-dose IFN-alpha exerts anti-angiogenic effects when used in the treatment of life-threatening hemangiomas of infancy, suggesting anti-angiogenesis as a mechanism of action. IFN-alpha may exert its anti-tumor effect in the setting of advanced malignancy by inhibiting the secretion of vascular endothelial growth factor (VEGF), a pro-angiogenic substance. We hypothesized that IFN-alpha would decrease the release of VEGF by melanoma tumors. We studied the effect of IFN-alpha on VEGF production in nine human melanoma cell lines. We also examined VEGF levels in 49 patients with advanced malignancies who received low-dose IFN-alpha and interleukin-12 (IL-12) on an NCI-sponsored phase I trial. Human melanoma cell lines produced varying amounts of VEGF in vitro (60-1500 pg/mL at 48 h). Certain melanoma cell lines such as 18105 MEL secreted low levels of VEGF (152 pg/mL) after 48 h of culture, whereas other lines secreted very high levels (FO-1 3,802 pg/mL). Treatment of melanoma cells with IFN-alpha (2000 U/mL) decreased VEGF secretion by 40-60% in VEGF-high cell lines; however, this effect was not demonstrated in VEGF-low cell lines. In cancer patients, pretreatment VEGF plasma levels varied from 471 to 4200 pg/mL. A decrease in VEGF plasma levels after treatment directly correlated with the number of treatment cycles administered (Pearson correlation, p = 0.04). In summary, IFN-alpha inhibits VEGF secretion by melanoma cell lines in vitro and may have similar actions in malignancies that respond to IFN-alpha treatment.
- Subjects :
- Cell Line, Tumor
Cell Proliferation drug effects
Humans
Interleukin-12 metabolism
Recombinant Proteins pharmacology
Vascular Endothelial Growth Factor A blood
Vascular Endothelial Growth Factor A metabolism
Interferon-alpha pharmacology
Melanoma metabolism
Skin Neoplasms metabolism
Vascular Endothelial Growth Factor A antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7465
- Volume :
- 28
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
- Publication Type :
- Academic Journal
- Accession number :
- 18771339
- Full Text :
- https://doi.org/10.1089/jir.2008.0118