Angiogenesis in endocrine tumors

Endocr Rev. 2003 Oct;24(5):600-32. doi: 10.1210/er.2002-0008.


Angiogenesis is the process of new blood vessel development from preexisting vasculature. Although vascular endothelium is usually quiescent in the adult, active angiogenesis has been shown to be an important process for new vessel formation, tumor growth, progression, and spread. The angiogenic phenotype depends on the balance of proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and inhibitors, as well as interactions with the extracellular matrix, allowing for endothelial migration. Endocrine glands are typically vascular organs, and their blood supply is essential for normal function and tight control of hormone feedback loops. In addition to metabolic factors such as hypoxia, the process of angiogenesis is also regulated by hormonal changes such as increased estrogen, IGF-I, and TSH levels. By measuring microvascular density, differences in angiogenesis have been related to differences in tumor behavior, and similar techniques have been applied to both benign and malignant endocrine tumors with the aim of identification of tumors that subsequently behave in an aggressive fashion. In contrast to other tumor types, pituitary tumors are less vascular than normal pituitary tissue, although the mechanism for this observation is not known. A relationship between angiogenesis and tumor size, tumor invasiveness, and aggressiveness has been shown in some pituitary tumor types, but not in others. There are few reports on the role of microvascular density or angiogenic factors in adrenal tumors. The mechanism of the vascular tumors, which include adrenomedullary tumors, found in patients with Von Hippel Lindau disease has been well characterized, and clinical trials of antiangiogenic therapy are currently being performed in patients with Von Hippel Lindau disease. Thyroid tumors are more vascular than normal thyroid tissue, and there is a clear correlation between increased VEGF expression and more aggressive thyroid tumor behavior and metastasis. Although parathyroid tissue induces angiogenesis when autotransplanted and PTH regulates both VEGF and MMP expression, there are few studies of angiogenesis and angiogenic factors in parathyroid tumors. An understanding of the balance of angiogenesis in these vascular tumors and mechanisms of vascular control may assist in therapeutic decisions and allow appropriately targeted treatment.

Publication types

  • Review

MeSH terms

  • Adrenal Gland Neoplasms / blood supply
  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Animals
  • Carcinoid Tumor / blood supply
  • Endocrine Gland Neoplasms / blood supply*
  • Gastrointestinal Neoplasms / blood supply
  • Humans
  • Matrix Metalloproteinases
  • Neovascularization, Pathologic* / genetics
  • Neuroendocrine Tumors / blood supply
  • Parathyroid Neoplasms / blood supply
  • Pituitary Neoplasms / blood supply
  • Thyroid Neoplasms / blood supply
  • Vascular Endothelial Growth Factor A


  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinases