Infantile Hemangioma: A Tumor Involving Hemogenic Endothelium with Erythropoetic Potential

Infantile hemangioma (IH) is a tumor of the microvasculature predominantly composed of proliferating endothelial cells, but also contains progenitor cells of mesenchymal and hematopoietic lineages. We have previously shown that IH has a primitive mesodermal origin. Here we investigated expression of hematopoietic associated proteins (Tal-1, GATA-2, CD133 & CD34) as well as the erythropoietin receptor (EPOR) and the embryonically-associated hemoglobin zeta chain (HBZ) by both the cells of the endothelium and the cells emanating from proliferating IH explants. Additionally we investigated if the cells emanating from the explants generate erythrocytes in vitro.

To investigate the expression of hematopoietic associated proteins and the primitive erythropoietic capacity of proliferating IH.

Proliferating IH biopsies from 5 patients were (i) processed for IHC staining for Tal-1, GATA-2, CD133, CD34, HBZ and EPOR; (ii) used to determine the relative expression of Tal-1, GATA-2, CD133, CD34, HBZ & EPOR transcripts by qRT-PCR; (ii) cultured as explants using our in vitro model and differentiated the cells down the erythropoietic lineage.

IHC showed that the cells that line the endothelium forming the capillaries of proliferating IH expressed Tal-1, GATA-2, CD133, CD34, HBZ and EPOR. qRT-PCR confirmed the IHC data as abundant expression mRNA transcripts for the same proteins was detected in both the tissue and the cells emanating from the cultured explants. Following 5 months in culture morphological biconcave cells were visible, and were confirmed to be erythrocytes by immunoreactivity to the erythrocyte-specific cell surface marker glycophorin A.

The mRNA and protein expression of hematopoietic associated proteins in proliferating IH supports our previous studies showing this tumor expressing markers of primitive mesoderm and confirms a hemogenic endothelium phenotype. The expression of the primitive erythropoiesis-associated proteins HBZ and EPOR by proliferating IH and its functional ability of proliferating IH explants to form erythrocytes in vitro confirms the erythropoietic potential. Proliferating IH thus represents an extra-medullary site of tumor-associated erythropoiesis.

No relevant conflicts of interest to declare.