The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy.
BACKGROUND
It is well established that tumors are dependent on angiogenesis for their growth and survival. Although uterine fibroids are known to be benign tumors with reduced vascularization, recent work demonstrates that the vasculature of fibroids is grossly and microscopically abnormal. Accumulating evidence suggests that angiogenic growth factor dysregulation may be implicated in these vascular and other features of fibroid pathophysiology.


METHODS
Literature searches were performed in PubMed and Google Scholar for articles with content related to angiogenic growth factors and myometrium/leiomyoma. The findings are hereby reviewed and discussed.


RESULTS
Multiple growth factors involved in angiogenesis are differentially expressed in leiomyoma compared with myometrium. These include epidermal growth factor (EGF), heparin-binding-EGF, vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-β and adrenomedullin. An important paradox is that although leiomyoma tissues are hypoxic, leiomyoma feature down-regulation of key molecular regulators of the hypoxia response. Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid development and growth. Notably, common treatments for fibroids such as GnRH agonists and uterine artery embolization (UAE) are shown to work at least partly via anti-angiogenic mechanisms.


CONCLUSIONS
Angiogenic growth factors play an important role in mechanisms of fibroid pathophysiology, including abnormal vasculature and fibroid growth and survival. Moreover, the fibroid's abnormal vasculature together with its aberrant hypoxic and angiogenic response may make it especially vulnerable to disruption of its vascular supply, a feature which could be exploited for treatment. Further experimental studies are required in order to gain a better understanding of the growth factors that are involved in normal and pathological myometrial angiogenesis, and to assess the potential of anti-angiogenic treatment strategies for uterine fibroids.
Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY 11219, USA.
Reshef
R
Tal
James H
JH
Segars
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology; D007889:Leiomyoma / Q000098:blood supply / Q000188:drug therapy / Q000209:etiology*; D009215:Myometrium / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology*; D014594:Uterine Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000209:etiology*; D014599:Uterus / Q000098:blood supply*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism / Q000502:physiology*
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D042442:Vascular Endothelial Growth Factors
angiogenesis; anti-angiogenesis; hypoxia; uterine leiomyoma; vasculature