A lesson for cancer research: placental microarray gene analysis in preeclampsia

Abstract

Tumor progression and pregnancy share many common features, such as immune tolerance and invasion. The invasion of trophoblasts in the placenta into the uterine wall is essential for fetal development, and is thus precisely regulated. Its deregulation has been implicated in preeclampsia, a leading cause for maternal and perinatal mortality and morbidity. Pathogenesis of preeclampsia remains to be defined. Microarray-based gene profiling has been widely used for identifying genes responsible for preeclampsia. In this review, we have summarized the recent data from the microarray studies with preeclamptic placentas. Despite the complex of gene signatures, suggestive of the heterogeneity of preeclampsia, these studies identified a number of differentially expressed genes associated with preeclampsia. Interestingly, most of them have been reported to be tightly involved in tumor progression. We have discussed these interesting genes and analyzed their potential molecular functions in preeclampsia, compared with their roles in malignancy development. Further investigations are warranted to explore the involvement in molecular network of each identified gene, which may provide not only novel strategies for prevention and therapy for preeclampsia but also a better understanding of cancer cells. The trophoblastic cells, with their capacity for proliferation and differentiation, apoptosis and survival, migration, angiogenesis and immune modulation by exploiting similar molecular pathways, make them a compelling model for cancer research.

Figure 1. Illustrative scheme of the common features shared by normal pregnancy and tumor development

While extravillous trophoblasts in the placenta are capable of migrating into the uterine decidua to establish appropriate nutrient and oxygen supply for the fetus development, malignant tumor cells have the capability to successfully invade their neighboring tissues to set up the friendly microenvironment for further progression. Moreover, both of them have the competence to establish effectively angiogenesis and to escape successfully the host immune defense system. In preeclampsia, however, trophoblasts fail to fulfill these tasks by showing defective invasion, altered angiogenesis and violent immune response. The interesting genes identified from the 18 microarray-based placental gene profiling are listed and described in the text. ST, syncytiotrophoblast; CT, cytotrophoblast. The figure design is inspired by Holtan et al, [4].