Editors' ChoiceAngiogenesis

PPARγ and the Placenta: Lessons That Could Inform Cancer Therapy

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Science Translational Medicine  22 Sep 2010:
Vol. 2, Issue 50, pp. 50ec145
DOI: 10.1126/scitranslmed.3001680

What do the placenta and metastatic cancer have in common? They both rely on angiogenesis (blood vessel formation) to advance their growth and development. However, unlike metastatic cancer placental angiogenesis is strictly regulated, in part by peroxisome proliferator–activated receptor γ (PPARγ).

PPARγ is a nuclear receptor that is highly expressed in fat tissue and plays a role in fat cell differentiation, as well as in glucose homeostasis and inflammation. PPARγ is also expressed in rodent and human placentas, but studies of its role in this organ have been limited by the fact that PPARγ-null mice (mice without the PPARγ gene) do not survive beyond embryonic day 9.5 to 11.5 because of abnormal placental blood vessel development. Nadra et al. have now developed a PPARγ-null mouse model that survived to birth, enabling examination of placental development through pregnancy and delivery.

Nadra et al. deleted PPARγ in the embryo but not in the placenta and demonstrated that these embryos were protected from the death that usually is seen in PPARγ-null mice. This finding suggested that a lack of placental expression was the cause of embryonic death. Additionally, the authors fed pregnant wild-type mice a PPARγ agonist and observed impairment in both placental and embryonic growth and development. Additional investigations confirmed a negative effect of the PPARγ agonist on placental angiogenesis, directly and through reducing proangiogenic factors such as proliferin.

This exciting series of investigations demonstrates how a lethal genetic defect can be overcome in order to enhance understanding of a biological process in a mouse model, which may lend insight into the process in humans: that is, a mechanism of action for termination of vascular proliferation at the end of pregnancy. In addition, these studies potentially provide lessons that could be applied to the control of other angiogenic processes, such as those that occur in the setting of metastatic cancer.

K. Nadra et al., PPARγ in placental angiogenesis. Endocrinology, 1 September 2010 (10.1210/en.2010-0131). [Abstract]

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