Effects of transforming growth factor-β1 on the proliferation and invasion of the HTR-8/SVneo cell line

Abstract

Transforming growth factor-β1 (TGF-β1) is involved in the regulation of trophoblast cell proliferation and invasion. However, the mechanism underlying this process remains unknown, which is predominantly due to the difficulty in obtaining and maintaining primary trophoblast cells in culture over a long period of time. The HTR-8/SVneo cell line is an immortalized trophoblast cell line, which has been reported to exhibit a number of similar characteristics to those of parental trophoblast cells. Therefore, the cell line has been a useful tool for the investigation of placental function and tumor progression. In the present study, the HTR-8/SVneo cell line was used as a model to investigate the TGF-β1/SMAD signaling pathway in the proliferation and invasion of trophoblast cells. The proliferation and invasion ability of HTR-8/SVneo cells was determined using the MTT and Transwell assays, respectively. In addition, reverse transcription polymerase chain reactions were performed to detect the mRNA expression of a panel of known downstream mediators of TGF-β1, including TGF-β receptor I (TβRI), SMAD4, SMAD3, SMAD7 and tissue inhibitor of metalloproteinases-1 (TIMP-1). The results indicated that TGF-β1 promotes the proliferation and invasion of the HTR-8/SVneo cell line at passage 90. Furthermore, the expression of TβRI, SMAD3 and SMAD4 were reduced following treatment with TGF-β1, while the expression of SMAD7 was increased and the expression of TIMP-1 remained unchanged following TGF-β1 treatment. These observations indicated that the effects of TGF-β1 on the proliferation and invasion of the HTR-8/SVneo cell line at passage 90 were different from those of parental trophoblasts, which is in contrast to the results of previous studies. It was concluded that the HTR-8/SVneo cell lines, which have been grown for over 90 passages, do not accurately represent parental trophoblast cells in studies of the TGF-β/SMAD signaling pathway.

miR-18a Contributes to Preeclampsia by Downregulating Smad2 (Full Length) and Reducing TGF-β Signaling

“…For instance, productions of TGF-β and Nodal, as well as their receptors, were significantly enhanced in PE placentas, which may lead to over-activated signaling, excessive cell apoptosis, and less invasion. 20 , 21 , 40 More importantly, in human placenta, TGF-β primarily regulates trophoblast cell invasion, 22 , 23 , 24 , 25 , 26 , 27 and Nodal promotes cell apoptosis. 41 We found that miR-18a increased cell invasiveness ( Figures 6 C and 6D) but did not influence the cell growth or cell cycle ( Figures 6 E and 6F).…”

“… 19 Furthermore, it is highly expressed in PE placentas, 20 , 21 and the dysregulation of its signaling pathway is responsible for the dysfunction of trophoblast cells and the pathophysiology of PE. 21 , 22 , 23 , 24 , 25 , 26 , 27 We therefore speculated that miR-18a interferes with the TGF-β signaling in PE placentas via targeting Smad2 and/or Smad3.…”

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

“…In this study, we isolated three different human MSC lines from Wharton's jelly of umbilical cord tissue of three female neonates and examined the effects of these hUCMSCs on the cellular functions of trophoblast cells. HTR-8/SVneo is an immortalized trophoblast cell line and is usually used to study villous trophoblast cells [ 15 – 17 ]. We thus used the HTR-8/SVneo cell line as a model to explore the influence of hUCMSCs on proliferation, migration, invasion, and secretion functions of trophoblast cells.…”

Inhibitory effect of dihydromyricetin on the proliferation of JAR cells and its mechanism of action

“…TGF-β activates TGF-β receptor (TβR)I and TβRII, resulting in the phosphorylation of receptor-regulated SMAD2/3, which is associated with the common mediator SMAD4. The SMAD2/3/4 complex is translocated to the nucleus, where it binds to DNA and regulates the transcription of several genes (31,32). Increased mRNA and protein expression levels of SMAD3 and SMAD4 promote cell proliferation, migration and invasion (33).…”