interleukin-8 and Hemangioma

Infantile hemangioma sometimes grows rapidly to a significant size around the first 2 months of life, which can be problematic and even destroy normal tissue. However, it is very difficult to predict the tumor growth at the first visit and to decide necessity of treatment. Therefore the identification of the biomarkers that can indicate a tendency to grow is clinically very important. In the present study, we evaluated the possibility that serum cytokine levels are available as the marker of hemangioma growth. Progressive hemangioma was defined as a lesion showing increased tumor size and/or coloration two weeks before and after the serum sampling, and we used membrane array to compare the twenty cytokine profiles between the sera of 3 progressive hemangioma patients and sex-/age-matched non-progressive hemangioma patients. As a result, many of the 20 cytokines were detected in the patients' sera. When a 2-fold difference in the mean levels of each group was considered meaningful, 6 of the 20 cytokines (IGF-1, IL-6, IL-8, PIGF, RANTES, TGF-β1) were down-regulated in the progressive hemangioma group compared to the non- progressive hemangioma group, and there were statistically significant difference (p < 0.05): especially, IGF-1, IL-6, IL-8, PIGF, and TGF-β1 did not expressed in all 3 progressive hemangioma patients. Accordingly, complicated cytokine network by these multiple cytokines may control the pathogenesis, and these cytokine levels may become clinically useful tumor markers. Furthermore, immunotherapy against them will be novel therapeutic approach.

Topics: Chemokine CCL5; Cytokines; Female; Hemangioma; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Interleukin-6; Interleukin-8; Transforming Growth Factor beta1

Hemangioma (HA) is tumor formed by hyper-proliferation of vascular endothelial cells. The roles of interleukins on the progression of HA are not well illustrated. Our present study revealed that the expression of interleukin -6 (IL-6) and IL-8 in HA cells were significantly increased as compared with that in the human umbilical vein endothelial cell (HUVEC) cells. Targeted inhibition of IL-6, while not IL-8, can significantly suppress the proliferation and migration of HA cells. IL-6 treatment can increase the expression of vascular endothelial growth factor A (VEGFA), while had no significant effect on the expression of basic fibroblast growth factor (bFGF), in HA cells. Deletion of VEGFA can abolish IL-6 induced progression of HA, suggesting the essential role of VEGFA in IL-6 induced HA development. The specific inhibitor of hypoxia-inducible factor (HIF)-1α, while not Sp1, NF-κB, or AP1, abolished IL-6 induced VEGFA expression. Over expression of HIF-1α can attenuate anti-IL-6 suppressed expression of VEGFA in HA cells. Furthermore, IL-6 triggered the expression, nuclear translocation, and transcription activities of HIF-1α in HA cells via increasing its binding with the signal transducer and activator of transcription-3 (STAT3). STAT3 inhibitor CPA7 or si-STAT3 can abolish IL-6 induced upregulation of HIF-1α in HDEC cells. Collectively, our study revealed that IL-6 can trigger the malignancy of HA cells via induction of proliferation and migration. The activation of STAT3/HIF-1α/VEGFA signal was essential for this process. It suggested that IL-6/STAT3/HIF-1α/VEGFA signal may represent a novel therapeutic target for human HA treatment.

Topics: Cell Line, Tumor; Cell Proliferation; Disease Progression; Down-Regulation; Hemangioma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; Interleukin-8; Signal Transduction; STAT3 Transcription Factor; Transcription, Genetic; Vascular Endothelial Growth Factor A