Expression Of Chemokine CXCL1/8 In Proliferating Infantile Hemangioma And The Effect Of Exogenous CXCL1/8 On Hemangioma Stem Cells

Object Infantille hemangioma（IH）is the most common benign tumor in infancy,and has been reported to affect up to 5%-10% of infants.IH usually develops early skin lesions in the first few weeks of birth,proliferates rapidly in the skin during the proliferating phase,and followed by involuting phase and involuted phase.Although the majority of cases were able to spontaneously regress without treatments,a small proportion of IH patients remain at risk of complications and poor prognosis without medical intervention.IH is characterized by the abnormal proliferation of endothelial cells and the abnormal vascular structure.The mechanism of the development of IH is not understood yet.Hemangioma stem cells（Hem SCs）are the cells with differentiation potential in IH tumors.Therefore,the study of Hem SCs is of great clinical significance.Chemokines are a class of small-molecule proteins with similar structures.In cancer,they play a key role in the migration pattern of immune cells to the tumor,thus shaping the immune characteristics of the tumor microenvironment.In addition,chemokines can directly target non-immune cells in the tumor microenvironment,including cancer,stromal cells,and vascular endothelial cells.Therefore,chemokines involve in multiple processes in tumor formation,such as angiogenesis,metastasis,cancer cell proliferation,migration,and invasion,which are key factors in disease progression and have a great impact on patient treatment and prognosis.Chemokines are also differentially expressed in the blood of IH patients,however the effect of chemokines on IH development has not been investigated.The experiment explored the expression of two chemokines in vivo and the influence of IH tissue on Hem SCs.Method Twenty pairs of proliferating IH tissue specimens in our hospital were collected,and immunohistochemistry was used to explore the expression of chemokine ligand（CXCL）1/8 in proliferating IH specimens.Hem SCs primary cells were sorted from proliferating IH tissues by CD133 immunomagnetic beads method,and the cells were collected for subsequent cell experiments.Five groups of different concentrations of CXCL1/8（0,10,20,50,100 ng/ml）were co-cultured with Hem SCs,and the effects of exogenous CXCL1/8 on Hem SCs were studied by cell viability and migration experiments.Result CXCL1/8 was expressed in proliferating IH interstitial tissue,but not in blood vessels.The overall expression of CXCL1/8 in proliferating IH was low,but the expression in intratumoral stromal tissue was higher than that in paratumoral stromal tissue.Compared with the control group without the addition of recombinant protein CXCL1 or CXCL8,the addition of CXCL1 or CXCL8 can promote the proliferation of Hem SCs.However,the addition of CXCL1 or CXCL8 had no effect on the migration ability of Hem SCs.Conclusion The expression of CXCL1/8 in the proliferating IH intratumor stroma was higher than that in the paratumor stroma.Exogenous CXCL1/8 could promote the proliferation of Hem SCs but had no effect on their migration ability.