Identification of signaling systems in proliferating and involuting phase infantile hemangiomas by genome-wide transcriptional profiling.
Infantile hemangiomas are characterized by rapid capillary growth during the first year of life followed by involution during early childhood. The natural history of these lesions creates a unique opportunity to study the changes in gene expression that occur in the vessels of these tumors as they proliferate and regress. Here we use laser capture microdissection and genome-wide transcriptional profiling of vessels from proliferating and involuting hemangiomas to identify differentially expressed genes. Relative to normal placental vessels, proliferating hemangiomas were characterized by increased expression of genes involved in endothelial-pericyte interactions, such as angiopoietin-2 (ANGPT2), jagged-1 (JAG1), and notch-4 (NOTCH4), as well as genes involved in neural and vascular patterning, such as neuropilin-2 (NETO2), a plexin domain containing receptor (plexinC1), and an ephrin receptor (EPHB3). Insulin-like growth factor binding protein-3 (IGFBP3) was down-regulated in proliferating hemangiomas. Involuting hemangiomas were characterized by the expression of chronic inflammatory mediators, such as the chemokine, stromal cell-derived factor-1 (SDF-1), and factors that may attenuate the angiogenic response, such as a member of the Down syndrome critical region (DSCR) family. The identification of genes differentially expressed in proliferating and involuting hemangiomas in vivo will contribute to our understanding of this vascular lesion, which remains a leading cause of morbidity in newborn children.
Department of Pathology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Monica L
ML
Calicchio
Tucker
T
Collins
Harry P
HP
Kozakewich
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015894:Genome, Human; D006391:Hemangioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007834:Lasers; D042282:Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm