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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis
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Endometriosis, angiogenesis and tissue factor.

Graciela Krikun1

  • 1Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, 333 Cedar Street, New Haven, CT 06510, USA.

Scientifica
|November 27, 2013
PubMed
Summary

Tissue factor (TF) plays a role in endometriosis. Targeting TF with the immunoconjugate Icon eradicated endometrial lesions in mice, suggesting a potential new therapy for endometriosis.

Area of Science:

  • Reproductive biology
  • Hemostasis
  • Oncology

Background:

  • Tissue factor (TF) initiates blood coagulation and is implicated in angiogenesis via protease-activated receptor-2 (PAR-2).
  • TF expression is altered in endometriosis, a condition involving endometrial tissue outside the uterus.

Purpose of the Study:

  • To review TF expression in normal and endometriosis-affected endometrium.
  • To investigate TF as a therapeutic target for endometriosis.

Main Methods:

  • Review of TF expression in human endometrial cells.
  • Treatment of a mouse model of endometriosis with a novel immunoconjugate (Icon).

Main Results:

  • TF expression is altered in eutopic and ectopic endometrial cells from women with endometriosis compared to normal endometrium.

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  • The immunoconjugate Icon eradicated endometrial lesions in a mouse model of endometriosis.
  • Fertility was not affected in the treated mice.

    • Conclusions:

    • Altered TF expression in endometriosis suggests it is a viable therapeutic target.
    • The immunoconjugate Icon demonstrates efficacy in eradicating endometriosis lesions without compromising fertility in a preclinical model.
    • These findings support the potential of TF-targeted therapies for human endometriosis treatment.