Helen E. Turner,
Adrian L. Harris,
Shlomo Melmed and
John A. H. Wass
Department of Endocrinology (H.E.T., J.A.H.W.), Churchill Hospital, Oxford OX3 7LJ, United Kingdom; Molecular Angiogenesis Group (A.L.H.), Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DU Oxford, United Kingdom; and Davis Research Institute (S.M.), Cedars Sinai Hospital, Los Angeles, California 90048
Correspondence: Address all correspondence and requests for reprints to: Dr. Helen E. Turner, Department of Endocrinology, Churchill Hospital, Old Road, Oxford OX3 7LJ, United Kingdom. E-mail: jenny.Thomson{at}orh.nhs.uk
Angiogenesis is the process of new blood vessel developmentfrom preexisting vasculature. Although vascular endotheliumis usually quiescent in the adult, active angiogenesis has beenshown to be an important process for new vessel formation, tumorgrowth, progression, and spread. The angiogenic phenotype dependson the balance of proangiogenic growth factors such as vascularendothelial growth factor (VEGF) and inhibitors, as well asinteractions with the extracellular matrix, allowing for endothelialmigration. Endocrine glands are typically vascular organs, andtheir blood supply is essential for normal function and tightcontrol of hormone feedback loops. In addition to metabolicfactors such as hypoxia, the process of angiogenesis is alsoregulated by hormonal changes such as increased estrogen, IGF-I,and TSH levels.
By measuring microvascular density, differences in angiogenesishave been related to differences in tumor behavior, and similartechniques have been applied to both benign and malignant endocrinetumors with the aim of identification of tumors that subsequentlybehave in an aggressive fashion.
In contrast to other tumor types, pituitary tumors are lessvascular than normal pituitary tissue, although the mechanismfor this observation is not known. A relationship between angiogenesisand tumor size, tumor invasiveness, and aggressiveness has beenshown in some pituitary tumor types, but not in others. Thereare few reports on the role of microvascular density or angiogenicfactors in adrenal tumors. The mechanism of the vascular tumors,which include adrenomedullary tumors, found in patients withVon Hippel Lindau disease has been well characterized, and clinicaltrials of antiangiogenic therapy are currently being performedin patients with Von Hippel Lindau disease. Thyroid tumors aremore vascular than normal thyroid tissue, and there is a clearcorrelation between increased VEGF expression and more aggressivethyroid tumor behavior and metastasis. Although parathyroidtissue induces angiogenesis when autotransplanted and PTH regulatesboth VEGF and MMP expression, there are few studies of angiogenesisand angiogenic factors in parathyroid tumors.
An understanding of the balance of angiogenesis in these vasculartumors and mechanisms of vascular control may assist in therapeuticdecisions and allow appropriately targeted treatment.
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