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Title: Differential expression of C/T antigens and 5-HT receptors in normotensive and pre-eclamptic placentae, and their role in trophoblast invasion
Author: Tamang, A. P.
ISNI:       0000 0004 5920 7903
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2015
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Cancer/testis (C/T) antigens are a unique class of tumour associated proteins that are prominently expressed in cancer cells of different histological origin. Placenta is one of the three non-cancerous tissues known to express these antigens. During the first trimester (FT) of pregnancy, placental invasion resembles to that in tumour, and is controlled by several vasoactive substances including 5-hydroxytryptamine (5-HT). Interestingly, in pre-eclampsia (a pregnancy related multi-system complication), the levels of 5-HT are found to be increased, whilst the overall trophoblast invasion is low, when compared to normal (NT) placenta. Previous studies have compared the status of factors that are involved in trophoblast invasion between NT and PE placenta. However, the expression patterns of all known 5-HT receptors in PE placentae have not been fully investigated, even though the 5-HT mediates its various actions via these receptors. Likewise, the status of C/T antigens which are also proposed to be involved in cancer cell proliferation, differentiation, migration and invasion in PE placentae is not known. On account of the differences in trophoblast invasion between NT and PE placenta, it was hypothesised that the expression of C/T antigens and 5-HT receptors vary. Also, since the circulating 5-HT is increased and the invasive potentials of trophoblast cells is decreased in PE, it was hypothesised the two events may influence one another. Therefore, this case controlled study, compared the C/T antigen and 5-HT receptor expression profiles amongst 11 FT, 13 NT, and 12 PE placentae. The study also focused on the effects of 5-HT on trophoblast invasion using placental cell lines. Significant differences in the status of the C/T antigens were found between NT and PE placentae using quantitative real-time PCR, western blotting and immunohistochemistry (IHC). Especially MAGEA1 (p < 0.0001) and MAGEA4 (p < 0.001) antigens are significantly up-regulated in PE placentae. Significant differences in expression were also observed between term (NT) and FT placentae. This is the first study to report the changes in both mRNA and proteins together with the cellular expression patterns of these C/T antigens in NT, PE and FT. On the 5-HT receptor side, 5-HT1B and 5-HT2B receptor were found to be significantly down-regulated in PE. Since very few studies looked at the effects of 5-HT in placental cells, the effects of 5-HT on migration/invasion using placental cell lines were also studied. 5-HT at 20 to 40μM, induced the migration and invasion of these cells. The expressions of the two 5-HT receptors and six C/T antigens, were also up-regulated at these concentrations. Thus, this study suggests 5-HT may be an important factor for trophoblast invasion. Hence, the shallow invasion in PE may be linked to the differential expression of 5-HT receptors and C/T antigens.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available