Abstract
Infantile hemangiomas are localized lesions comprised primarily of aberrant endothelial cells. COSMC plays a crucial role in blood vessel formation and is characterized as a molecular chaperone of T-synthase which catalyzes the synthesis of T antigen (Galβ1,3GalNAc). T antigen expression is associated with tumor malignancy in many cancers. However, roles of COSMC in infantile hemangioma are still unclear. In this study, immunohistochemistry showed that COSMC was upregulated in proliferating hemangiomas compared with involuted hemangiomas. Higher levels of T antigen expression were also observed in the proliferating hemangioma. Overexpression of COSMC significantly enhanced cell growth and phosphorylation of AKT and ERK in human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of COSMC with siRNA inhibited endothelial cell growth. Mechanistic investigation showed that O-glycans were present on VEGFR2 and these structures were modulated by COSMC. Furthermore, VEGFR2 degradation was delayed by COSMC overexpression and facilitated by COSMC knockdown. We also showed that COSMC was able to regulate VEGF-triggered phosphorylation of VEGFR2. Our results suggest that COSMC is a novel regulator for VEGFR2 signaling in endothelial cells and dysregulation of COSMC expression may contribute to the pathogenesis of hemangioma.
Highlights
Infantile hemangiomas are characterized by an aberrant growth of endothelial cells in the infant age
We observed that COSMC expression in the surrounding normal blood vessels was not detectable or relatively weak, similar to that found in involuted hemangiomas (Fig. S1)(if accepted, production will need this reference to link the reader to the figure)
These findings suggest that COSMC is overexpressed in proliferating hemangiomas compared with involuted hemangiomas which entails that COSMC may play a role in hemangioma development
Summary
Infantile hemangiomas are characterized by an aberrant growth of endothelial cells in the infant age. They are the most common tumors in infants and children. The incidence is ranged from 1.1 to 2.6%, with the highest estimates approaching 10 to 12% [1]. The life cycle of hemangiomas differs from that of most tumors in that it progresses from a phase of rapid proliferation followed by spontaneous involution [2]. Hemangiomas are composed of densely packed endothelial cells that form small capillaries [2]. While in the involuting phase, the capillaries have larger lumens with thickened capillary basement membranes, less-plump endothelial cells, and fibrofatty replacements of the lesion [3]
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