Analyses of selected tumour-associated factors expression in normotensive and preeclamptic placenta.

Abstract

Human placenta is often considered a controlled-tumour because of shared properties such as invasion and angiogenesis. We assessed the status of a few selected tumour-associated factors (TAFs) in late onset pre-eclamptic (PE) and normotensive (NT) placentae, to understand their involvement in trophoblast invasion. These molecules include aldehyde dehydrogenase (ALDH3A1), aurora kinases (AURK-A/C), platelet derived growth factor receptor-α (PDGFRα), jagged-1 (JAG1) and twist related protein-1 (TWIST1). The expression of TAF was compared in 13 NT and 11 PE (late onset) placentae using immunoblotting/immunohistochemistry. We then used a novel spheroidal cell model developed from transformed human first trimester trophoblast cell lines HTR8/SVneo and TEV-1 to determine the expression and localization of these six factors during invasion. We also compared the expression of these TAFs during migration and invasion. Our results suggest that expressions of ALDH3A1, AURK-A, PDGFRα, and TWIST1 are significantly upregulated in PE placentae (p<0.05) when compared to NT placentae, whereas AURK-C and JAG1 are down-regulated (p<0.05). The protein expression pattern of all the six factors were found to be similar in spheroids in comparison to their parental counterparts. The invasive potential of the spheroids was also enhanced when compared with the parental cells. Collectively, data from our present study suggests that these TAFs are involved in placental invasion and their altered expressions may be regarded as a compensatory mechanism against reduced invasion.