Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis
AUTOR(ES)
Ritter, Matthew R.
FONTE
The National Academy of Sciences
RESUMO
Hemangiomas are benign tumors of the vascular endothelium and are the most common tumors of infancy. These tumors are characterized by an initial phase of rapid proliferation, which is followed, in most cases, by spontaneous involution. Although most lesions resolve without complication, there are some cases in which hemangiomas can be life threatening when occurring near a vital structure. Treatment for these aggressive tumors represents an unmet clinical need. In addition, this characteristic progression of hemangiomas through distinct phases provides a unique opportunity for studying endothelial cell biology and angiogenesis. Using DNA microarrays representing approximately 10,000 human genes, we identified insulin-like growth factor 2 (IGF-2) as a potentially important regulator of hemangioma growth. IGF-2 was highly expressed during the proliferative phase and substantially decreased during involution. This finding was confirmed at the message level by quantitative reverse transcription–PCR and at the protein level by immunohistochemistry. IGF-2 protein was localized primarily to tumor vessels or vascular channels. Using a human hemangioma explant model, we show that IGF-2 promotes sprouting from intact hemangioma tissue. In addition, several angiogenesis-related factors, including integrins αvβ3 and α5β1, are present in proliferating hemangiomas. During the involuting phase, an increase in several IFN-induced genes was observed. These studies identify potential regulators of hemangioma growth and involution and provide a foundation on which to build further mechanistic investigations into angiogenesis, using hemangiomas as a model.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124252Documentos Relacionados
- Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous.
- Regulation of insulin-like growth factor I gene expression by growth hormone.
- Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function
- The receptor for insulin-like growth factor II mediates an insulin-like response.
- Insulin-like growth factor-1 stimulation of lymphopoiesis.