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Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis

Academic Article
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Overview

related to degree

  • Dorrell, Michael, Ph.D. in Biomedical Research, Scripps Research 1998 - 2003

authors

  • Ritter, M. R.
  • Dorrell, Michael
  • Edmonds, J.
  • Friedlander, Sheila
  • Friedlander, Martin

publication date

  • May 2002

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • 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 alpha(v)beta3 and alpha5beta1, 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.

subject areas

  • Cell Division
  • Child
  • Child, Preschool
  • Endothelium, Vascular
  • Gene Expression Regulation, Neoplastic
  • Hemangioma
  • Humans
  • Infant
  • Insulin-Like Growth Factor II
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger
  • Receptors, Fibronectin
  • Receptors, Vitronectin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
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Identity

PubMed Central ID

  • PMC124252

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.102185799

PubMed ID

  • 12032304
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Additional Document Info

start page

  • 7455

end page

  • 7460

volume

  • 99

issue

  • 11

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