Evidence by molecular profiling for a placental origin of infantile hemangioma

Abstract

The origin of the pathogenic endothelial cells in common infantile hemangioma is unknown. We show here that the transcriptomes of human placenta and infantile hemangioma are sufficiently similar to suggest a placental origin for this tumor, expanding on recent immunophenotypical studies that have suggested this possibility [North, P. E., et al. (2001) Arch. Dermatol. 137, 559 -570]. The transcriptomes of placenta, hemangioma, and eight normal and diseased tissues were compared by hierarchical and nonhierarchical clustering analysis of >7,800 genes. We found that the level of transcriptome similarity between placenta and hemangioma exceeded that of any other tissue compared and paralleled that observed between a given tissue and its derived tumor, such as normal and cancerous lung. The degree of similarity was even greater when a subset of endothelial cell-specific genes was analyzed. Genes preferentially expressed in both placenta and hemangiomas were identified, including 17-␤ hydroxysteroid dehydrogenase type 2 and tissue factor pathway inhibitor 2. These data demonstrate the value of global molecular profiling of tissues as a tool for hypothesis-driven research. Furthermore, it suggests that the unique self-limited growth of infantile hemangioma may, in fact, mirror the lifetime of placental endothelium.angiogenesis ͉ endothelium ͉ microarray ͉ gene array

Identification of Signaling Systems in Proliferating and Involuting Phase Infantile Hemangiomas by Genome-Wide Transcriptional Profiling

“…17,18 Additionally, molecular profiling suggested a placental origin for infantile hemangioma. 19 However, none of these studies used genome wide arrays and typically involved preparing transcript from random samples of the resected tumor. To more precisely define patterns of gene expression in proliferating and involuting hemangiomas, we used laser capture microdissection (LCM) to selectively isolate the lesional vessels and avoid missing molecular events that are masked by studying random samples from the resected specimen.…”

Current Concepts in the Pathogenesis and Management of Vascular Lesions - A Brief Review.

“…However, infantile hemangiomas most likely arise from hematopoietic 1471 progenitor cells (from placenta or stem cell) in the appropriate milieu of genetic alterations and cytokines. (10) Abnormal levels of matrix metalloproteinases (MMP-9) and proangiogenic factors (VEGF, b-FGF, and TGF-beta 1) play a role in hemangioma pathogenesis. (11) Genetic errors in growth factor receptors have also been shown to affect development of hemangiomas.…”

Pyogenic granuloma, an impaired wound healing process, linked to vascular growth driven by FLT4 and the nitric oxide pathway

“…Simultaneously, the latter test detected an additional set of 15 genes shared by the placenta and infantile hemangiomas, a likely finding as genetic similarities between infantile hemangioma and placenta are known. 14,15 Among these 15 genes, one observed genes implicated in angiogenesis, CLU 16 and FST 17 as well as imprinted genes, such as DIO3 and DLK1. The latter are part of the mir-379/mir-656 miRNA cluster, a chromosomal region that appears increasingly more relevant to normal placental development [17][18][19] and fetal growth, 20 stem cell differentiation 21 and various pathological conditions.…”